Elisabetta Panza

University of Naples Federico II, Napoli, Campania, Italy

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Publications (16)60.57 Total impact

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    ABSTRACT: In human two main metabolic enzymes synthesize hydrogen sulfide (H2S): cystathionine γ lyase (CSE) and cystathionine β synthase (CBS). A third enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) synthesize H2S in the presence of the substrate 3-mercaptopyruvate (3-MP). The immunohistochemistry analysis performed on human melanoma samples demonstrated that CSE expression was highest in primary tumors, decreased in the metastatic lesions and was almost silent in non lymph node metastases. The primary role played by CSE was confirmed by the finding that the over-expression of CSE induced spontaneous apoptosis of human melanoma cells. The same effect was achieved by using different H2S donors and, among them, the most active resulted to be diallyl trisulfide (DATS). The main pro-apoptotic mechanisms involved were suppression of nuclear factor-κB activity and inhibition of AKT and extracellular signal-regulated kinase pathways. A proof of concept was obtained in vivo by using a murine melanoma model. In fact, either L-cysteine, the CSE substrate, or DATS inhibited tumor growth in mice. In conclusion, we have defined that the L-cysteine/CSE/H2S pathway is involved in melanoma progression.This article is protected by copyright. All rights reserved.
    Pigment Cell & Melanoma Research 09/2014; · 5.84 Impact Factor
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    ABSTRACT: Nutritional research has shifted recently from alleviating nutrient deficiencies to chronic disease prevention. We investigated the activity of indicaxanthin, a bioavailable phytochemical of the betalain class from the edible fruit of Opuntia ficus-indica (L. Miller) in a rat model of acute inflammation. Rat pleurisy was achieved by injection of 0.2 mL of λ-carrageenin in the pleural cavity, and rats were killed 4, 24, and 48 h later; exudates were collected to analyze inflammatory parameters, such as nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α); cells recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) expression, and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation. Indicaxanthin (0.5, 1, or 2 μmol/kg), given orally before carrageenin, time- and dose-dependently, reduced the exudate volume (up to 70%) and the number of leukocytes recruited in the pleural cavity (up to 95%) at 24 h. Pretreatment with indicaxanthin at 2 μmol/kg inhibited the carrageenin-induced release of PGE2 (91.4%), NO (67.7%), IL-1β (53.6%), and TNF-α (71.1%), and caused a decrease of IL-1β (34.5%), TNF-α (81.6%), iNOS (75.2%), and COX2 (87.7%) mRNA, as well as iNOS (71.9%) and COX-2 (65.9%) protein expression, in the recruited leukocytes. Indicaxanthin inhibited time- and dose- dependently the activation of NF-κB, a key transcription factor in the whole inflammatory cascade. A pharmacokinetic study with a single 2 μmol/kg oral administration showed a maximum 0.22 ± 0.02 μmol/L (n = 15) plasma concentration of indicaxanthin, with a half-life of 1.15 ± 0.11 h. When considering the high bioavailability of indicaxanthin in humans, our findings suggest that this dietary pigment has the potential to improve health and prevent inflammation-based disorders.
    Journal of Nutrition 12/2013; · 4.23 Impact Factor
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    ABSTRACT: Here we have characterized perthamide C, a cyclopeptide from a Solomon Lithistid sponge Theonella swinhoei, which displays an anti-inflammatory/immunomodulatory activity. The study has been performed using the carragenan-induced mouse paw edema that displays an early (0-6 h) and a late phase (24-96 h). Perthamide C significantly inhibits neutrophils infiltration in tissue both in the early and late phases. This effect was coupled to a reduced expression of the endothelial nitric oxide synthase (eNOS) in the early phase while cyclooxygenase-1 and 2 (COX-1, COX-2), and inducible NOS (iNOS) expression were unaffected. In the late phase perthamide C reduced expression of both NOS isoforms without affecting COXs expression. This peculiar selectivity toward the two enzymes deputed to produce NO lead us to investigate on a possible action of perthamide C on lymphocytes infiltration and activation. We found that perthamide C inhibited the proliferation of peripheral lymphocytes, and that this effect was secondary to its metabolic activation in vivo. Indeed, in vitro perthamide C did not inhibit proliferation as opposite to its metabolite perthamide H. In conclusion, perthamide C selectively interferes with NO generation triggered by either eNOS or iNOS without affecting either COX-1 or COX-2. This in turn leads to modulation of the inflammatory response through a reduction of vascular permeability, neutrophil infiltration as well as lymphocyte proliferation.
    PLoS ONE 03/2013; 8(3):e57801. · 3.53 Impact Factor
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    ABSTRACT: Background Hydrogen sulphide (H2S) is a novel gaseous mediator enzymatically produced by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE). It is involved in physiological homeostatic processes and several pathological conditions; however, more importantly, H2S has a prominent role in cardiovascular system, where CSE deletion results in hypertension [1].ACE inhibitors are widely used in controlling blood pressure in hypertensive patients and they represent first line treatment in different cardiovascular diseases, since they also show additional beneficial effects unrelated to ACE inhibition and .In particular, therapeutic use of zofenopril, a sulfhydrylated ACE inhibitor, has raised hypothesis over a potential role of thiol group in such beneficial effects, other than antioxidant activity.Here, we aimed to investigate on vascular effect of zofenoprilat, water-soluble metabolite of zofenopril, with respect to H2S pathway activation. Methods In order to pursue our goal, we performed isolated organ bath experiments by using aorta and carotid arteries harvested from Wistar Kyoto rats, where we tested vascular effect of zofenoprilat, compared to other ACE inhibitors, in presence of CSE inhibitor PAG or after endothelium removal.In addition, we also performed in vivo experiment, where we tested vascular response after two weeks treatment with zofenopril compared to enalapril in spontaneously hypertensive rats.We also determined vascular response tol-cys, precursor for H2S production, and quantified H2S levels in plasma and tissues and CSE and CBS protein levels upon different treatments. Results In vitro data showed that zofenoprilat, but not enalaprilat, was able to relax both aorta and carotid arteries in a concentration dependent fashion (100 nM–1 mM), reaching ∼60% vasodilation in both cases.Endothelium removal significantly reduced zofenoprilat induced vasorelaxation in aorta (EC50:8.5 μM vs 381 μM), but this effect was not observed in carotid.Next, CSE inhibition by PAG nearly abrogated zofenoprilat vasodilation in both aorta and carotid, indicating a role for H2S in this effect.In vivo data, first highlighted a significantly stronger effect of zofenopril vs enalapril treatment in lowering blood pressure (p < 0.05).In addition, vascular reactivity, determined as response to Ach or phenylephrine, was better restored by zofenopril than enalapril administration.Furthermore, vasorelaxant response to l-cys was significantly improved in zofenopril vs enalapril treated animals (p < 0.05) and levels of circulating H2S were restored by zofenopril only.At the same extent, only zofenopril treatment restored CSE, but not CBS, expression in aorta after two weeks treatment, while a slight and not significant increase was observed in carotid artery. Conclusion In conclusion, we show that sulfhydrylated ACE inhibitor zofenopril triggers H2S pathway and regulates different signal transduction cascades, other than inhibition of ACE. We suggest that this action could be, at least partly, explicative of the additional effects reported in the clinical literature about sulfhydrylated ACE inhibitors. Our data also imply the chance to understand, by using a drug already adopted in clinic, the role played by the l-Cys/H2S pathway in human hypertension.
    Nitric Oxide 09/2012; 27:S18. · 3.18 Impact Factor
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    ABSTRACT: Background Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. The incidence of MH reactions ranges from 1:5000 to 1:50,000 anesthesias, however genetic abnormalities have been estimated as great as one in 3000 subjects [1]. The symptoms of MH include hyperthermia, increase in carbon dioxide production and oxygen consumption, muscle rigidity, rhabdomyolisis, tachycardia and, if untreated, death. Over 90 mutations have been identified in the ryanodine receptor (RYR1) gene and at least 30 are causal for MH. Thegenetic test only detects about 30% of people at riskof MH. Therefore, the “gold standard” for MH diagnosis is the in vitro contracture test. These tests enclose a positive response to caffeine, which is a well-known non specific PDE inhibitor [2], and to halothane, whose mechanism of action involves KATP channels [3]. Since these actions are among the most accredited molecular mechanisms triggered by H2S and we aimed to evaluate the role of H2S/L-Cys pathway in MH. Methods The procedure is performed accordingly to the “European Group protocol for investigation of malignant hyperthermia susceptibly” Briefly, the muscular biopsy of the vastus group of the quadriceps muscle is harvested under regional anaesthesia. Eight muscular bundles of 15–25 mm length and 2–3 mm thickness are placed in a tissue bath with Krebs solution at 37 °C and connected to an isometric transducer. Electrical stimulus is than applied and the muscle is stretched slowly up to 2 g. After20 min of equilibration caffeine or halothane are added in the tissue bath at progressive concentrations. An increase in resting tension of at least 2 mN allows a MH susceptible (MHS) diagnosis. After diagnosis has been made, muscle bundles from both MHS and MH negative (MHN) subjects have been used for functional studies. Western blot analysis, qRT-PCR for H2S molecular machinery and plasmatic and tissutal H2S content were also performed. Results H2S assay performed on tissues homogenate revealed an significant increase of H2S content in MHS patients compared to MHN. Conversely, no difference was founded in plasmatic levels H2S of both groups of patients. Western blot analysis showed a significant and selective increase of CBS expression in MHS patients compared to MHN, confirmed by qRT-PCR analysis. Functional studies performed on MHN showed that pre-incubation of the tissue with NaHS was able to switch an MHS typical response following challenge with either caffeine or halothane. Conclusion Our data show that in MHS patients there is an increase in CBS expression that accounts for the enhanced concentration of H2S within the skeletal muscle. The involvement of H2S in MH is further confirmed by the finding that incubation of MHN tissues with NaHS prior to the addition of either caffeine or halothane generates a response similar to MHS tissues. In conclusion we demonstrate that L-Cys/CBS/H2S pathway is involved in malygnant hyperthermia. This finding may allows a different diagnostic and/or therapeutic approach.
    Nitric Oxide 09/2012; 27:S27–S28. · 3.18 Impact Factor
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    ABSTRACT: Background The need for new drugs in melanoma treatment is of great relevance. Indeed, current therapies for the treatment of metastatic melanoma offer a limited clinical benefit and only in recent years there has been an advancement due to the identification of new molecular targets [1]. Hydrogen sulphide (H2S) is endogenously produced by the action of three enzymes CBS, CSE and the newly discovered 3-MST [2]. While H2S is cytoprotective at physiological concentrations, it seems to have pro-apoptotic actions in cancer cells [3]. However, to date there are not definitive reports on the role played by H2S in cancer development. Aim of this study was to determine the possible involvement of H2S in human melanoma. Methods The study has been performed by using some relevant human melanoma cell lines such as A375, WM115 and SK-Mel-28. HaCat, a normal human fibroblast cell line, has been used as control. Cellular proliferation was evaluated by the MTT assay. Apoptosis was assayed by flow cytometry analysis by double staining with Annexin V and propidium iodide (PI). NF-kB/DNA-binding activity was evaluated by electrophoretic mobility shift assay. Expression of CBS, CSE, 3-MST was assayed by quantitative real time RT-PCR, expression of Bcl-2, XIAP, c-FLIP, caspase 3, PARP, IKBa and Akt/p-Akt was determined by western blotting. Levels of H2S in the supernatant and in total cellular extracts were assayed by colorimetric assay. Results Diallyl trisulfide (DATS) is a garlic-derived polysulfide able to release H2S [4]. Our results demonstrate that DATS greatly suppressed, in a time and concentration-dependent manner, proliferation of the three human melanoma cell lines used. The most striking effect was obtained on the A375 cell line whose proliferation was inhibited, following incubation with DATS (10–30–100 μM, 72 h) by 30%, 70%, and 78% respectively (p < 0.001). This effect well correlated with the significant increase in H2S levels found in both supernatants and cellular lysates. Conversely, DATS up to 300 μM did not affect proliferation of HaCat. DATS-induced inhibition of A375 proliferation (10–100 μM, 72 h) was almost completely reversed by haemoglobin (10 μM; p < 0.001) a scavenger of H2S. Moreover, DATS-induced inhibition of A375 proliferation was due to the induction of apoptosis as demonstrated by FACS analysis with Annexin V/PI staining and further confirmed by the inhibition of Bcl-2, XIAP, FLIP, as well as by the cleavage and consequent activation of caspase-3 and inactivation of poly (ADP ribose) polymerase (PARP-1). Constitutive NF-kB and activated Akt expression have been described in melanoma[5]. We also demonstrated that H2S released by DATS suppressed both constitutive NF-kB/DNA-binding activity and Akt phosphorylation suggesting that the apoptotic effect observed following exposure to H2S was consistent with the signal transduction pathways activated. Conclusion In conclusion, we demonstrate that H2S triggers, in relevant human melanoma cell lines, an apoptotic effect. This effect, in turn, activates downstream a signal pattern that candidates H2S as a possible novel therapeutic/target or diagnostic tool.
    Nitric Oxide 09/2012; 27:S28–S29. · 3.18 Impact Factor
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    ABSTRACT: Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded two new alkaloids, named sinulasulfoxide (1) and sinulasulfone (2), characterized by an amide linkage between a phytanic acid moiety and an uncommon sulfur-containing unit. Their complete stereostructures were elucidated by interpretation of MS and NMR data along with CD analysis and chemical modifications. Sinulasulfoxide (1) proved to moderately inhibit LPS-induced NO release.
    Tetrahedron Letters 07/2012; 53(30):3937–3939. · 2.39 Impact Factor
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    ABSTRACT: Ring strain causes planar chirality in tedarenes A and B, two cyclic diarylheptanoids isolated from the marine sponge Tedania ignis. In both molecules, the chiral plane is an olefinic system, which is very rare among natural products. In tedarene A (1), interconversion is too fast to allow isolation of the enantiomeric atropisomers but still slow enough to cause coalescence of some (1)H and (13)C NMR signals at room temperature. In tedarene B (2), which also shows stable central and axial chirality, the two planar diastereomers are in slow equilibrium. Tedarene B is the smallest natural product with central, axial, and planar chirality in the same simple molecule. The identification of planar chirality as the difference between its conformational isomers allowed the use of theoretical prediction of the CD spectrum to determine the absolute configuration of the stereogenic carbon C-9 as well as of the biphenyl chiral axis.
    The Journal of Organic Chemistry 03/2012; 77(15):6377-83. · 4.64 Impact Factor
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    ABSTRACT: Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded a known glucosylcerebroside of the sarcoehrenoside-type and sinularioside (2), a new naturally triacetylated glycolipid containing two α-D-arabinopyranosyl residues and a myristyl alcohol unit. Their complete stereostructures were solved by interpretation of MS and NMR data along with CD analysis of degradation products. Sinularioside proved to moderately inhibit LPS-induced NO release, providing interesting clues into the poorly understood structure-activity relationships for anti-inflammatory glycolipids.
    Bioorganic & medicinal chemistry letters 03/2012; 22(8):2723-5. · 2.65 Impact Factor
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    ABSTRACT: Well-defined amphiphilic Y-shaped miktoarm star-block copolymers of PEO and PCL were synthesized by ring-opening polymerization of ε-caprolactone initiated by a PEO-bound lysine macroinitiator. The copolymers were characterized by (1)H NMR, SEC, DSC, and WAXD techniques. Separate PCL and PEO crystalline phases occur in melt-crystallized copolymers when their segmental lengths were comparable and the PCL content was ≤80 wt %. Self-assembling of these copolymers in aqueous medium led to nanoaggregates with low critical aggregation concentration values (0.35 to 1.6 mg·L(-1)) and size depending on composition. Despite the fact that copolymers were not prone to self-organize in vesicles, once processed by a novel w/o emulsion-melting-sonication technique, they gave nanocapsules with a water core and a hydrophilic surface. A macromolecular fluorescent dye was effectively loaded and released at sustained rate by optimizing nanocapsule formulation. The results demonstrate that amphiphilic block copolymers can be assembled in different kinds of nanomorphologies independently of their hydrophilic/hydrophobic balance and architecture through specifically designed preparation techniques.
    Biomacromolecules 11/2011; 12(12):4221-9. · 5.79 Impact Factor
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    ABSTRACT: Chemical analysis of the Indonesian soft coral Sinularia sp. (order Alcyonacea, family Alcyoniidae) afforded two known and three new C-4 norcembranoids, named chloroscabrolides A (3) and B (4) and prescabrolide (5). Chloroscabrolide A is a pentacyclic norcembranoid including an unprecedented THF-type ring to connect C-13 and C-15; furthermore, it is only the second chlorinated cembranoid derivative to be reported in the literature. The relative configuration of chloroscabrolide A has been established on the basis of a comparison between experimental 13C NMR data and DFT-calculated 13C NMR chemical shifts. All the isolated norcembranoids have been evaluated for iNOS protein inhibition.
    Tetrahedron 10/2011; 67(41):7983-7988. · 2.82 Impact Factor
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    ABSTRACT: Malignant melanoma is a highly aggressive tumor that frequently resists chemotherapy, so the search for new agents for its treatment is of great importance. In the present study, the antiproliferative propensity against human melanoma cell lines of lauroside B (1), a megastigmane glycoside isolated from Laurus nobilis (bay laurel) leaves, was investigated. This compound suppressed the proliferation of three human melanoma cell lines, namely, A375, WM115, and SK-Mel-28. The 1-induced inhibition of human melanoma cell proliferation was due to the induction of apoptosis, as demonstrated by FACS analysis with annexin V/PI staining and confirmed by activation of caspase-3 and by the cleavage of poly(ADP-ribose) polymerase (PARP). Growing evidence implicates NF-κB as an important contributor to metastasis and increased chemoresistance of melanoma. Thus, it was hypothesized that 1-induced apoptosis could be associated with suppression of NF-κB activation. The results showed that exposure of human melanoma cells to 1 inhibited IκB-α degradation and constitutive NF-κB DNA-binding activity as well as the expression, regulated by NF-κB, of two antiapoptotic genes, XIAP and c-FLIP. Induction of apoptosis by 1 in human aggressive melanoma cell lines has a potential high biological value.
    Journal of Natural Products 12/2010; 74(2):228-33. · 3.95 Impact Factor
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    ABSTRACT: Terpioside B (2a), a unique glycolipid containing two fucose residues in the furanose form in its pentasaccharide chain, was isolated from the marine sponge Terpios sp. Its complete stereostructure was solved by interpretation of mass spectrometric and NMR data along with CD and GG-MS analyses of its degradation products. Terpioside B is a potent inhibitor against LPS-induced NO release, and is considerably more active than simpler glycosphingolipids such as terpioside A and monoglucosylceramide.
    Bioorganic & medicinal chemistry 07/2010; 18(14):5310-5. · 2.82 Impact Factor
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    ABSTRACT: Changes in the expression of potassium channels regulate skeletal muscle development. The purpose of this study was to investigate the expression profile and pharmacological role of K(v)7 voltage-gated potassium channels in skeletal muscle differentiation, proliferation, and survival after myotoxic insults. Transcripts for all K(v)7 genes (K(v)7.1-K(v)7.5) were detected by polymerase chain reaction (PCR) and/or real-time PCR in murine C(2)C(12) myoblasts; K(v)7.1, K(v)7.3, and K(v)7.4 transcripts were up-regulated after myotube formation. Western blot experiments confirmed K(v)7.2, K(v)7.3, and K(v)7.4 subunit expression, and the up-regulation of K(v)7.3 and K(v)7.4 subunits during in vitro differentiation. In adult skeletal muscles from mice and humans, K(v)7.2 and K(v)7.3 immunoreactivity was mainly localized at the level of intracellular striations positioned between ankyrinG-positive triads, whereas that of K(v)7.4 subunits was largely restricted to the sarcolemmal membrane. In C(2)C(12) cells, retigabine (10 microM), a specific activator of neuronally expressed K(v)7.2 to K(v)7.5 subunits, reduced proliferation, accelerated myogenin expression, and inhibited the myotoxic effect of mevastatin (IC(50) approximately 7 microM); all these effects of retigabine were prevented by the K(v)7 channel blocker 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991) (10 muM). These data collectively highlight neural K(v)7 channels as significant pharmacological targets to regulate skeletal muscle proliferation, differentiation, and myotoxic effects of drugs.
    Journal of Pharmacology and Experimental Therapeutics 03/2010; 332(3):811-20. · 3.89 Impact Factor
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    ABSTRACT: In this study, the functional consequences of the pharmacological modulation of the M-current (IKM) on cytoplasmic Ca2+ intracellular Ca2+concentration ([Ca2+]i) changes and excitatory neurotransmitter release triggered by various stimuli from isolated rat cortical synaptosomes have been investigated. Kv7.2 immunoreactivity was identified in pre-synaptic elements in cortical slices and isolated glutamatergic cortical synaptosomes. In cerebrocortical synaptosomes exposed to 20 mM [K+]e, the IKM activator retigabine (RT, 10 μM) inhibited [3H]d-aspartate ([3H]d-Asp) release and caused membrane hyperpolarization; both these effects were prevented by the IKM blocker XE-991 (20 μM). The IKM activators RT (0.1–30 μM), flupirtine (10 μM) and BMS-204352 (10 μM) inhibited 20 mM [K+]e-induced synaptosomal [Ca2+]i increases; XE-991 (20 μM) abolished RT-induced inhibition of depolarization-triggered [Ca2+]i transients. The P/Q-type voltage-sensitive Ca2+channel (VSCC) blocker ω-agatoxin IVA prevented RT-induced inhibition of depolarization-induced [Ca2+]i increase and [3H]d-Asp release, whereas the N-type blocker ω-conotoxin GVIA failed to do so. Finally, 10 μM RT did not modify the increase of [Ca2+]i and the resulting enhancement of [3H]d-Asp release induced by [Ca2+]i mobilization from intracellular stores, or by store-operated Ca2+channel activation. Collectively, the present data reveal that the pharmacological activation of IKM regulates depolarization-induced [3H]d-Asp release from cerebrocortical synaptosomes by selectively controlling the changes of [Ca2+]i occurring through P/Q-type VSCCs.
    Journal of Neurochemistry 02/2009; 109(1):168 - 181. · 4.24 Impact Factor
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    ABSTRACT: KCNQ2 and KCNQ3 subunits encode for the muscarinic-regulated current (I(KM)), a sub-threshold voltage-dependent K+ current regulating neuronal excitability. In this study, we have investigated the involvement of I(KM) in dopamine (DA) release from rat striatal synaptosomes evoked by elevated extracellular K+ concentrations ([K+]e) and by muscarinic receptor activation. [3H]dopamine ([3H]DA) release triggered by 9 mmol/L [K+]e was inhibited by the I(KM) activator retigabine (0.01-30 micromol/L; Emax = 54.80 +/- 3.85%; IC50 = 0.50 +/- 0.36 micromol/L). The I(KM) blockers tetraethylammonium (0.1-3 mmol/L) and XE-991 (0.1-30 micromol/L) enhanced K+-evoked [3H]DA release and prevented retigabine-induced inhibition of depolarization-evoked [3H]DA release. Retigabine-induced inhibition of K+-evoked [3H]DA release was also abolished by synaptosomal entrapment of blocking anti-KCNQ2 polyclonal antibodies, an effect prevented by antibody pre-absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic agonist oxotremorine (OXO) (1-300 micromol/L) potentiated 9 mmol/L [K+]e-evoked [3H]DA release (Emax = 155 +/- 9.50%; EC50 = 25 +/- 1.80 micromol/L). OXO (100 micromol/L)-induced [3H]DA release enhancement was competitively inhibited by pirenzepine (1-10 nmol/L) and abolished by the M3-preferring antagonist 4-diphenylacetoxy N-methylpiperidine methiodide (1 micromol/L), but was unaffected by the M1-selective antagonist MT-7 (10-100 nmol/L) or by Pertussis toxin (1.5-3 microg/mL), which uncouples M2- and M4-mediated responses. Finally, OXO-induced potentiation of depolarization-induced [3H]DA release was not additive to that produced by XE-991 (10 micromol/L), was unaffected by retigabine (10 micromol/L), and was abolished by synaptosomal entrapment of anti-KCNQ2 antibodies. Collectively, these findings indicate that, in rat striatal nerve endings, I(KM) channels containing KCNQ2 subunits regulate depolarization-induced DA release and that I(KM) suppression is involved in the reinforcement of depolarization-induced DA release triggered by the activation of pre-synaptic muscarinic heteroreceptors.
    Journal of Neurochemistry 08/2007; 102(1):179-93. · 4.24 Impact Factor

Publication Stats

91 Citations
60.57 Total Impact Points


  • 2007–2014
    • University of Naples Federico II
      • • Department of Pharmacy
      • • Department of Neuroscience and Reproductive and Odontostomatological Sciences
      Napoli, Campania, Italy
    • Catholic University of the Sacred Heart
      • Institute of Pharmacology
      Roma, Latium, Italy
  • 2009
    • Università degli Studi del Molise
      • Department of Health Sciences (S.Pe.S.)
      Campobasso, Molise, Italy