R Serio

Università degli Studi di Palermo, Palermo, Sicily, Italy

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Publications (102)262.82 Total impact

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    ABSTRACT: Although an extensive body of literature confirmed γ-aminobutyric acid (GABA) as mediator within the enteric nervous system (ENS) controlling gastrointestinal (GI) function, the true significance of GABAergic signalling in the gut is still a matter of debate. GABAergic cells in the bowel include neuronal and endocrine-like cells, suggesting GABA as modulator of both motor and secretory GI activity. GABA effects in the GI tract depend on the activation of ionotropic GABAA and GABAC receptors and metabotropic GABAB receptors, resulting in a potential noteworthy regulation of both the excitatory and inhibitory signalling in the ENS. However, the preservation of GABAergic signalling in the gut could not be limited to the maintenance of physiologic intestinal activity. Indeed, a series of interesting studies have suggested a potential key role of GABA in the promising field of neuroimmune interaction, being involved in the modulation of immune cell activity associated with different systemic and enteric inflammatory conditions. Given the urgency of novel therapeutic strategies against chronic immunity-related pathologies, i.e. multiple sclerosis and Inflammatory Bowel Disease, an in-depth comprehension of the enteric GABAergic system in health and disease could provide the basis for new clinical application of nerve-driven immunity. Hence, in the attempt to drive novel researches addressing both the physiological and pathological importance of the GABAergic signalling in the gut, we summarized current evidence on GABA and GABA receptor function in the different parts of the GI tract, with particular focus on the potential involvement in the modulation of GI motility and inflammation. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Pharmacological research : the official journal of the Italian Pharmacological Society. 12/2014;
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    ABSTRACT: We have previously demonstrated that menthol reduces murine gastric tone in part through a neural mechanism, involving adrenergic pathways and reduction of ongoing release of acetylcholine from enteric nerves. In the present study we aimed to verify whether the gastric relaxation to menthol may be triggered by interaction with neural receptors or ionic channels proteins, such as transient receptor potential (TRP)-melastatin8 (TRPM8), TRP-ankyrin 1 (TRPA1), 5-hydroxytriptamine 3 (5-HT3) receptor or cholinergic nicotinic receptors. Spontaneous mechanical activity was detected in vitro as changes in intraluminal pressure from isolated mouse stomach. Menthol (0.3-30mM) induced gastric relaxation which was not affected by 5-benzyloxytryptamine, a TRPM8 receptor antagonist, HC030031, a TRPA1 channel blocker. In addition, allylisothiocyanate, a TRPA1 agonist, but not (2S,5R)-2-Isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboximide, a selective TRPM8 agonist, induced gastric relaxation. Genic expression of TRPA1, but not of TRPM8, was revealed in mouse stomach. Indeed, menthol-induced gastric relaxation was significantly reduced by hexamethonium, cholinergic nicotinic receptor antagonist. Menthol, at concentrations that failed to affect gastric tone, reduced the contraction induced by dimethylphenylpiperazinium, nicotinic receptor agonist. The joint application of hexamethonium and atropine, muscarinc receptor antagonist, or hexamethonium and phentholamine, α-adrenergic receptor antagonist, did not produce any additive reduction of the relaxant response to menthol. Lastly, ondansetron, a 5-HT3 receptor antagonist, was ineffective. In conclusion, our study suggests that nicotinic receptors, but not TRP and 5-HT3 receptors, are molecular targets for menthol inducing murine gastric relaxation, ultimately due to the reduction of acetylcholine release from enteric nerves. Copyright © 2014 Elsevier B.V. All rights reserved.
    European journal of pharmacology. 10/2014; 745C:129-134.
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    ABSTRACT: We investigated the role of GABA on intestinal motility using as model the murine distal colon. Effects induced by GABA receptor recruitment were examined in whole colonic segments and isolated circular muscle preparations to analyze their influence on peristaltic reflex and on spontaneous and neurally-evoked contractions. Using a modified Trendelenburg set-up, rhythmic peristaltic contractions were evoked by gradual distension of the colonic segments. Spontaneous and neurally-evoked mechanical activity of circular muscle strips were recorded in vitro as changes in isometric tension. GABA, at low concentrations (10-50µM), potentiated peristaltic activity and the neural cholinergic contractions, whilst it, at higher concentrations (500µM - 1mM), had inhibitory effects. GABA excitatory effects were mimicked by muscimol, GABAA-receptor agonist, and prevented by bicuculline, GABAA-receptor antagonist, which per se reduced peristaltic activity and the cholinergic contractile responses. Inhibitory effects were mimicked by baclofen, GABAB-receptor agonist, and antagonized by phaclofen, GABAB-receptor antagonist and by hexamethonium, neural nicotinic receptor. Guanethidine was ineffective on GABA effects. Non-cholinergic responses were not affected by GABA agents. All drugs failed to affect the response to carbachol. Lastly, GABAC receptor agonist/antagonist had any effect on colonic motility. In conclusion, GABA in mouse distal colon is a modulator of peristaltic activity via the regulation of acetylcholine release from cholinergic neurons through interaction with GABAA or GABAB receptors. GABAA receptors are recruited at low GABA concentrations, increasing acetylcholine release and propulsive activity. At high GABA concentrations the activation of GABAB receptors overrides GABAA receptor effects, decreasing acetylcholine release and peristaltic activity.
    European journal of pharmacology 03/2014; · 2.59 Impact Factor
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    ABSTRACT: In this paper, we describe the preparation of liver-targeted polymeric micelles potentially able to carry sorafenib to hepatocytes for treatment of hepatocarcinoma (HCC), exploiting the presence of carbohydrate receptors, ASGPR. These micelles were prepared starting from a galactosylated polylactide-polyaminoacid conjugate. This latter was obtained by chemical reaction of α,β-poly(N-2-hydroxyethyl) (2-aminoethylcarbamate)-d,l-aspartamide (PHEA-EDA) with polylactic acid (PLA), and subsequent reaction with lactose, leading to PHEA-EDA-PLA-GAL copolymer. Liver-targeted sorafenib-loaded micelles were obtained in aqueous media at low PHEA-EDA-PLA-GAL copolymer concentration value with nanometer size and slightly positive zeta potential. Biodistribution studies on mice demonstrated, after oral administration of sorafenib loaded PHEA-EDA-PLA-GAL micelles, the preferential sorafenib accumulation into the liver. This finding raises hope in terms of future drug delivery strategy of sorafenib-loaded micelles targeted to the liver for the HCC treatment.
    International Journal of Pharmaceutics 03/2014; · 3.99 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP-1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP-1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous glucagon-like peptide 1 (GLP-1), to analyze the mechanism of action and to verify the presence of GLP-1 receptors in human colon circular muscular strips. Organ bath technique, RT-PCR, Western blotting and immunofluorescence were used. In human colon, exogenous GLP-1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9-39), a GLP-1 receptor antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, neural blocker, or Nω-nitro-L-arginine, a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP-1 receptor in the human colon. Double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP-1 receptor was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP-1 receptor is expressed in the human colon and, once activated by exogenous GLP-1, mediates an inhibitory effect on large intestine motility through nitric oxide neural release.
    Journal of Endocrinology 01/2014; · 4.06 Impact Factor
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    ABSTRACT: The aim of this study was to analyze whether arginine vasopressin (AVP) may be considered a modulator of intestinal motility. In this view, we evaluated, in vitro, the effects induced by exogenous administration of AVP on the contractility of mouse distal colon, the subtype(s) of receptor(s) activated and the action mechanism. Isometric recordings were performed on longitudinal and circular muscle strips of mouse distal colon. AVP (0.001 nM-100 nM) caused concentration-dependent contractile effects only on the longitudinal muscle, antagonized by the V1 receptor antagonist, V-1880. AVP-induced effect was not modified by tetrodotoxin, atropine indomethacin. Contractile response to AVP was reduced in Ca(2+)-free solution or in the presence nifedipine, and it was abolished by depletion of calcium intracellular stores after repetitive addition of carbachol in calcium-free medium with addition of cyclopiazonic acid. U-73122, an inhibitor of the phospholipase C, effectively antagonized AVP effects, whilst it was not affected by an adenylyl cyclase inhibitor. Oxytocin induced an excitatory effect in the longitudinal muscle of distal colon at very high concentrations, effect antagonized by V-1880. The results of this study shown that AVP, via activation of V1 receptors, is able to modulate positively contractile activity of longitudinal muscle of mouse distal colon, independently by enteric nerve activation and prostraglandin synthesis. Contractile response is achieved by increase in cytoplasmatic Ca(2+) concentration via extracellular Ca(2+) influx from L-type Ca(2+) channels and via Ca(2+) release from intracellular stores through phospholipase C pathway. No modulation has been observed on the contractility of the circular muscle.
    Regulatory Peptides 10/2013; · 2.06 Impact Factor
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    ABSTRACT: Menthol, the main active constituent of peppermint oil, exerts gut spasmolytic effects, although its mechanism of action remains unclear. We investigated the effects of menthol on gastric emptying and spontaneous- or evoked- mechanical activity of whole murine stomach. Gastric emptying was calculated after i.p. administration of menthol (50mg/Kg). Responses induced by menthol on gastric intraluminal pressure and evoked-cholinergic contractions were analysed in vitro. Menthol decreased the gastric emptying rate. In vitro, menthol (0.3-30mM) produced a concentration-dependent relaxation of whole stomach, that was significantly reduced by tetrodotoxin or ω-conotoxin GVIA. The gastric relaxant responses were not affected by Nω-nitro-L-arginine methyl ester, inhibitor of nitric oxide-synthase, apamin or [Lys1,Pro2,5,Arg3,4,Tyr6]vasoactive intestinal peptide (VIP)(7-28), a VIP receptor antagonist, but they were significantly antagonized by atropine or guanethidine, a blocker of adrenergic neurotransmission. The joint application of atropine and guanethidine did not produce any additive effects on menthol effects. Phentolamine, an α-adrenoceptor antagonist, but not propranolol, a β-adrenoceptor antagonist, significantly reduced menthol responses and the contemporary administration of both adrenergic antagonists did not produce additive effects. Menthol (1-100μM) produced a reduction of the electrically-evoked cholinergic contractions, which was prevented by guanethidine. Menthol did not affect the contractions induced by carbachol. In conclusion, menthol in mouse, is able to reduce the rate of gastric emptying and to relax the stomach in vitro. The latter effect appears due, almost in part, to neural mechanisms, with involvement of α-adrenoceptors leading to reduction of tonic ongoing release of acetylcholine.
    European journal of pharmacology 09/2013; · 2.59 Impact Factor
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    ABSTRACT: The aim of the present study was to evaluate if guanine-based purines may affect the gastric motor function in mouse. Thus, the influence of guanosine on the gastric emptying rate in vivo was determined and its effects on spontaneous gastric mechanical activity, detected as changes of the intraluminal pressure, were analyzed in vitro before and after different treatments. Gastric gavage of guanosine (1.75-10 mg/kg) delayed the gastric emptying. Guanosine (30 μM-1 mM) induced a concentration-dependent relaxation of isolated stomach, which was not affected by the inhibition of the purine nucleoside phosphorylase enzyme by 4'-deaza-1'-aza-2'-deoxy-1'-(9-methylene)-immucillin-H. The inhibitory response was antagonized by S-(4-nitrobenzyl)-6-thioinosine, a membrane nucleoside transporter inhibitor, but not affected by 9-chloro-2-(2-furanyl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine, a nonselective adenosine receptor antagonist, or by tetrodotoxin, a blocker of neuronal voltage-dependent Na(+) channels. Moreover, guanosine-induced effects persisted in the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase or tetraethylammonium, a nonselective potassium channel blocker, but they were progressively reduced by increasing concentrations of 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor. Lastly, the levels of cyclic adenosine monophosphate (cAMP), measured by ELISA, in gastric full thickness preparations were increased by guanosine. In conclusion, our data indicate that, in mouse, guanosine is able to modulate negatively the gastric motor function, reducing gastric emptying and inducing muscular relaxation. The latter is dependent by its cellular uptake and involves adenylyl cyclase activation and increase in cAMP intracellular levels, while it is independent on neural action potentials, adenosine receptors, and K(+) channel activation.
    Purinergic Signalling 07/2013; · 2.64 Impact Factor
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    ABSTRACT: AimThis study investigates whether a local renin–angiotensin system (RAS) exists in mouse colon and whether angiotensin II (Ang II) may play a role in the regulation of the contractile activity. Methods Isometric recordings were performed in vitro on the longitudinal muscle of mouse proximal and distal colon. Transcripts encoding for RAS components were investigated by RT-PCR. ResultsAng II caused, in both preparations, a concentration-dependent contractile effect, antagonized by losartan, AT1 receptor antagonist, but not by PD123319, AT2 receptor antagonist. The combination of losartan plus PD123319 caused no change on the Ang II-induced contraction than losartan alone. Tetrodotoxin, neural blocker, reduced the contractile response to Ang II in the proximal colon, whilst the response was abolished in the distal colon. In both preparations, atropine, muscarinic receptor antagonist, or SR140333, NK1 receptor antagonist, reduced the Ang II responses. Ondansetron, 5-HT3 receptor antagonist, SR48968, NK2 receptor antagonist, or hexamethonium, nicotinic receptor antagonist, were ineffective. The joint application of atropine and SR140333 produced no additive effect. Atropine reduced NK1-induced contraction. Transcripts encoding RAS components were detected in the colon samples. However, just AT1A mRNA was expressed in both preparations, and AT2 mRNA was expressed only in the distal colon. Conclusion In the murine colon, local RAS may play a significant role in the control of contractile activity. Ang II positively modulates the spontaneous contractile activity via activation of post-junctional and pre-junctional AT1A receptors, the latter located on the enteric neurones, modulating the release of tachykinins and acetylcholine.
    Acta Physiologica 02/2013; 207(2). · 4.38 Impact Factor
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    ABSTRACT: We investigated the potential anorectic action of peripherally administered glucagon-like peptide 2 (GLP2) in lean and diet-induced obese (DIO) mice. Mice, fasted for 16 h, were injected i.p. with native GLP2 or [Gly2]GLP2, stable analog of GLP2, before or after GLP2 (3-33), a GLP2 receptor (GLP2R) antagonist, or exendin (9-39), a GLP1R antagonist. Food intake was measured at intervals 1, 2, 4, 8, and 24 h postinjection. In addition, we tested in lean mice the influence of [Gly2]GLP2 on gastric emptying and the effects of GLP1 alone or in combination with [Gly2]GLP2 on food intake. [Gly2]GLP2 dose dependently and significantly inhibited food intake in lean and DIO mice. The reduction of food intake occurred in the first hour postinjection and it was sustained until 4 h postinjection in lean mice while it was sustained until 2 h postinjection in DIO mice. GLP2 significantly inhibited food intake in both lean and DIO mice but only in the first hour postinjection. The efficiency of [Gly2]GLP2 or GLP2 in suppressing food intake was significantly weaker in DIO mice compared with lean animals. The [Gly2]GLP2 anorectic actions were blocked by the GLP2R antagonist GLP2 (3-33) or by the GLP1R antagonist exendin (9-39). The coadministration of [Gly2]GLP2 and GLP1 did not cause additive effects. [Gly2]GLP2 decreased the gastric emptying rate. Results suggest that GLP2 can reduce food intake in mice in the short term, likely acting at a peripheral level. DIO mice are less sensitive to the anorectic effect of the peptide.
    Journal of Endocrinology 03/2012; 213(3):277-84. · 4.06 Impact Factor
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    ABSTRACT: We investigated the possible modulation of the intestinal contractility by uracil nucleotides (UTP and UDP), using as model the murine small intestine. Contractile activity of a mouse ileum longitudinal muscle was examined in vitro as changes in isometric tension. Transcripts encoding for uracil-sensitive receptors was investigated by RT-PCR. UDP induced muscular contractions, sensitive to PPADS, suramin, or MRS 2578, P2Y(6) receptor antagonist, and mimicked by PSB 0474, P2Y(6)-receptor agonist. UTP induced biphasic effects characterized by an early inhibition of the spontaneous contractile activity followed by muscular contraction. UTP excitatory effects were antagonized by PPADS, suramin, but not by MRS 2578, whilst the inhibitory effects were antagonized by PPADS but not by suramin or MRS 2578. UTPγS, P2Y(2)/(4) receptor agonist but not 2-thio-UTP, P2Y(2) receptor agonist, mimicked UTP effects. The inhibitory effects induced by UTP was abolished by ATP desensitization and increased by extracellular acidification. UDP or UTP responses were insensitive to TTX, atropine, or L-NAME antagonized by U-73122, inhibitor of phospholipase C (PLC) and preserved in the presence of nifedipine or low Ca(2+) solution. Transcripts encoding the uracil nucleotide-preferring receptors were expressed in mouse ileum. Functional postjunctional uracil-sensitive receptors are present in the longitudinal muscle of the mouse ileum. Activation of P2Y(6) receptors induces muscular contraction, whilst activation of P2Y(4) receptors leads to inhibition of the contractile activity. Indeed, the presence of atypical UTP-sensitive receptors leading to muscular contraction is suggested. All uracil-sensitive receptors are linked to the PLC pathway.
    Purinergic Signalling 11/2011; 8(2):275-85. · 2.64 Impact Factor
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    ABSTRACT: Adenosine is considered to be an important modulator of intestinal motility. This study was undertaken to investigate the role of adenosine in the modulation of contractility in the mouse duodenum and to characterize the adenosine receptor subtypes involved. RT-PCR was used to investigate the expression of mRNA encoding for A(1), A(2A), A(2B) and A(3) receptors. Contractile activity was examined in vitro as changes in isometric tension. In mouse duodenum, all four classes of adenosine receptors were expressed, with the A(2B) receptor subtype being confined to the mucosal layer. Adenosine caused relaxation of mouse longitudinal duodenal muscle; this was antagonized by the A(1) receptor antagonist and mimicked by N(6) -cyclopentyladenosine (CPA), selective A(1) agonist. The relaxation induced by A(1) receptor activation was insensitive to tetrodotoxin (TTX) or N(ω) -nitro-l-arginine methyl ester (l-NAME). Adenosine also inhibited cholinergic contractions evoked by neural stimulation, effect reversed by the A(1) receptor antagonist, but not myogenic contractions induced by carbachol. CPA and 2-p-(2-carboxyethyl) phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride hydrate (CGS-21680), A(2A) receptor agonist, both inhibited the nerve-evoked cholinergic contractions. l-NAME prevented only the CGS-21680-induced effects. S-(4-Nitrobenzyl)-6-thioinosine, a nucleoside uptake inhibitor, reduced the amplitude of nerve-evoked cholinergic contractions, an effect reversed by an A(2A) receptor antagonist or l-NAME. Adenosine can negatively regulate mouse duodenal motility either by activating A(1) inhibitory receptors located post-junctionally or controlling neurotransmitter release via A(1) or A(2A) receptors. Both receptors are available for pharmacological recruitment, even if only A(2A) receptors appear to be preferentially stimulated by endogenous adenosine.
    British Journal of Pharmacology 05/2011; 164(6):1580-9. · 5.07 Impact Factor
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    ABSTRACT: Recently, we have showed that indicaxanthin, the yellow betalain pigment abundant in the fruit of Opuntia ficus indica, has remarkable spasmolytic effects on the intestinal contractility in vitro. Thus, the purpose of the present study was to investigate the mechanism of action underlying the observed response. We used organ bath technique to record the mechanical activity of the mouse ileum longitudinal muscle and ELISA to measure the levels of cAMP. Indicaxanthin induced inhibitory effects on spontaneous mechanical activity, which were unaffected by indomethacin, a non-selective inhibitor of cycloxygenase; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor of nitric oxide-dependent guanylyl cyclase; 2'5'dideoxyadenosine, an adenylyl cyclase inhibitor; and zaprinast, a selective inhibitor of the cGMP phosphodiesterase isoenzyme. Indicaxanthin effects were reduced significantly in the presence of 3-isobutyl-1-methylxanthine (IBMX), a non selective inhibitor of phosphodiesterases (PDEs). Indicaxanthin and IBMX significantly reduced the carbachol-evoked contractions and the joint application of both drugs did not produce any additive effect. Indicaxanthin and IBMX increased the inhibitory effects of forskolin, an adenylyl cyclase activator, and the joint application of both drugs did not produce any additive effect. Indicaxanthin, contrarily to IBMX, did not affect the inhibitory action of sodium nitroprusside, a soluble guanylyl cyclase activator. Indicaxanthin increased both basal and forskolin-induced cAMP content of mouse ileal muscle. The present data show that indicaxanthin reduces the contractility of ileal longitudinal muscle by inhibition of PDEs and increase of cAMP concentration and raise the possibility of using indicaxanthin in the treatment of motility disorders, such as abdominal cramps.
    European journal of pharmacology 02/2011; 658(2-3):200-5. · 2.59 Impact Factor
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    ABSTRACT: Adenine-based purines play a pivotal role in the control of gastrointestinal motility in rodents. Recently, guanine-based purines have been also shown to exert extracellular effects in the central nervous system raising the possibility of the existence of distinct receptors for guanine-based purines. Thus, it seems likely to speculate that also guanine-based purines may play a role in the modulation of the intestinal contractility. Spontaneous and neurally-evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips from mouse distal colon. Guanosine up to 3mM or guanine up to 1mM failed to affect the spontaneous mechanical activity, but reduced the amplitude of the electrical field stimulation (EFS)-induced cholinergic contractions, without affecting the early nitrergic relaxation. Both compounds failed to affect the direct contractile responses evoked by carbachol. No desensitization of the response was observed. Guanine-based purine effects were not altered by theophylline, P1 purinoceptor antagonist, by PPADS or suramin, P2 purinoceptor antagonists, by ODQ, guanilyl cyclase inhibitor, or by DDA, adenylyl cyclase inhibitor. Nucleoside uptake inhibitors, dipyridamole or 6-[(4-Nitrobenzyl)thio]-9-β-D-ribofuranosylpurine (NBTI), antagonized the inhibitory effects induced by guanosine without interfering with guanine. On the contrary, adenine, a competitive inhibitor of nucleobase uptake, antagonized guanine-induced effects. In conclusion, our data indicate that guanosine and guanine are able to modulate negatively the excitatory cholinergic neurotransmission in the circular muscle layer of mouse colon. Guanine-based purines appear to interfere with prejunctional acethylcoline release. Their effects are dependent by their cellular uptake, and independent by adenine-based purine receptors.
    European journal of pharmacology 10/2010; 650(1):350-5. · 2.59 Impact Factor
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    ABSTRACT: We investigated, using an organ bath technique, the effects of a hydrophilic extract from Opuntia ficus indica fruit pulp (cactus fruit extract, CFE) on the motility of mouse ileum, and researched the extract component(s) responsible for the observed responses. CFE (10-320 mg of fresh fruit pulp equivalents/mL of organ bath) reduced dose-dependently the spontaneous contractions. This effect was unaffected by tetrodotoxin, a neuronal blocker, N(omega)-nitro-l-arginine methyl ester, a nitric oxide synthase blocker, tetraethylammonium, a potassium channel blocker, or atropine, a muscarinic receptor antagonist. CFE also reduced the contractions evoked by carbachol, without affecting the contractions evoked by high extracellular potassium. Indicaxanthin, but not ascorbic acid, assayed at concentrations comparable with their content in CFE, mimicked the CFE effects. The data show that CFE is able to exert direct antispasmodic effects on the intestinal motility. The CFE inhibitory effects do not involve potassium channels or voltage-dependent calcium channels but rather pathways of calcium intracellular release. The fruit pigment indicaxanthin appears to be the main component responsible for the CFE-induced effects.
    Journal of Agricultural and Food Chemistry 07/2010; 58(13):7565-71. · 3.11 Impact Factor
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    ABSTRACT: The aims of the present study were to investigate, using mouse whole stomach in vitro, the effects of gamma-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by phaclofen, GABA(B)-receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA(C)-receptor antagonist. Muscimol, GABA(A)-receptor agonist, mimicked GABA effects inducing relaxation, which was significantly reduced by bicuculline, N omega-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthase or apamin, inhibitor of small conductance Ca(2+)-dependent K(+) channels, which blocks the purinergic transmission in this preparation. It was abolished by tetrodotoxin (TTX) or l-NAME plus apamin. Baclofen, a specific GABA(B)-receptor agonist, induced an increase in the gastric tone, which was antagonized by phaclofen and abolished by TTX or atropine. Bicuculline, but not phaclofen or TPMPA, per se induced an increase in gastric tone, which was prevented by L-NAME. In conclusion, our results suggest that GABA is involved in the regulation of mouse gastric tone, through modulation of intrinsic neurons. Activation of GABA(A)-receptors mediates relaxation through neural release of NO and neurotransmitters, activating Ca(2+)-dependent K(+) channels, likely purines, while activation of GABA(B)-receptors leads to contraction through acetylcholine release.
    Neuropharmacology 06/2010; 58(7):1033-7. · 4.11 Impact Factor
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinal motility through vagal afferents and central nervous mechanisms; however, no data is available about a direct influence on the gastrointestinal wall. Our aim was to investigate the effects of GLP-1 on the spontaneous and evoked mechanical activity of mouse duodenum and colon and to identify the presence and distribution of GLP-1 receptors (GLP-1R) in the muscle coat. Organ bath recording technique and immunohistochemistry were used. Glucagon-like peptide-1 (up to the concentration of 1 mumol L(-1)) failed to affect spontaneous mechanical activity. It caused concentration-dependent reduction of the electrically evoked cholinergic contractions in circular smooth muscle of both intestinal segments, without affecting the longitudinal muscle responses. Glucagon-like peptide-1 inhibitory effect was significantly antagonized by exendin (9-39), an antagonist of GLP-1R. In both intestinal preparations, GLP-1 effect was not affected by guanethidine, a blocker of adrenergic neurotransmission, but it was significantly reduced by N(omega)-nitro-l-arginine methyl ester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractions evoked by exogenous carbachol. Immunohistochemistry demonstrated GLP-1R expression in the enteric neurons. Furthermore, 27% of GLP-1R immunoreactive (IR) neurons in the duodenum and 79% of GLP-1R-IR neurons in the colon, co-expressed nNOS. The present results suggest that GLP-1 is able to act in the enteric nervous system by decreasing the excitatory cholinergic neurotransmission through presynaptic GLP-1Rs, which modulate NO release.
    Neurogastroenterology and Motility 02/2010; 22(6):664-e203. · 2.94 Impact Factor
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    ABSTRACT: Since the role of dopamine in the bowel motility is far from being clear, our aim was to analyse pharmacologically the effects of dopamine on mouse ileum contractility. Contractile activity of mouse ileum was examined in vitro as changes in isometric tension. Dopamine caused a concentration-dependent reduction of the spontaneous contraction amplitude of ileal muscle up to their complete disappearance. SCH-23390, D1 receptor antagonist, which per se increased basal tone and amplitude of spontaneous contractions, antagonized the responses to dopamine, whilst sulpiride or domperidone, D2 receptor antagonists, were without effects. The application of both D1 and D2 antagonists had additive effects. SKF-38393, D1 receptor agonist, mimicked dopamine-induced effects. Dopamine responses were insensitive to tetrodotoxin, atropine, nitric oxide synthase inhibitor or adenosine receptor antagonists, but they were reduced by adenylyl cyclase inhibition or apamin. Dopamine at a concentration which did not cause a significant reduction of phasic contractions inhibited the cholinergic contractions in response to field stimulation. SCH-23390 per se induced an increase of the neural cholinergic contraction and antagonized the dopamine effects, whilst sulpiride or domperidone did not. The application of D1 and D2 antagonists had additive effects. In conclusion, mouse ileum is under basal inhibitory control by dopamine, through D1 receptor activation, linked to adenylyl cyclase and activation of apamin-sensitive potassium channels. An agonistic interaction of the dopamine receptor subtypes in the regulation intestinal contractility has being also highlighted. This study would provide new insight on the pharmacology of the modulation of the gastrointestinal contractility by dopamine.
    Pharmacological Research 02/2010; 61(5):371-8. · 4.35 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
  • Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor

Publication Stats

756 Citations
262.82 Total Impact Points

Institutions

  • 1987–2014
    • Università degli Studi di Palermo
      • Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche
      Palermo, Sicily, Italy
  • 2005
    • Accademia delle Scienze di Medicina Palliativa
      Bolonia, Emilia-Romagna, Italy
  • 1988–1990
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada