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Publications (13)28.21 Total impact

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    ABSTRACT: Adenosine 5'-triphosphate (ATP) may be an important neurotransmitter in the gastrointestinal tract. The present study examined the motor effects of exogenous ATP on longitudinally-oriented preparations of the guinea-pig isolated ileum and the influence of drugs on the ATP-induced responses. High micromolar concentrations of ATP caused two types of contraction, a phasic, cholinergic response and a tonic, tetrodotoxin-resistant contraction. The phasic contraction was reduced by hexamethonium (5x10(-5) M), but left uninfluenced by capsaicin tachyphylaxis or tachyphylaxis to alpha,beta-methylene ATP. The tonic response was resistant to atropine, hexamethonium, capsaicin, omega-conotoxin GVIA, or pretreatment with alpha,beta-methylene ATP. Both types of ATP-induced contraction were diminished or abolished by the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 3x10(-6) and 3x10(-5) M, respectively). In the precontracted, atropine-treated ileum ATP (10(-6)-10(-4) M) caused guanethidine-resistant relaxation. This response was not influenced by tetrodotoxin, omega-conotoxin GVIA, or NG-nitro-L-arginine, but was abolished by apamin (10(-7) M), and inhibited by PPADS (3x10(-5) M) or reactive blue 2 (10(-5) M), in a surmountable manner. A high degree of tachyphylaxis was observed with the relaxant effect of ATP (10(-5)-10(-4) M). A high concentration (3x10(-4) M) of PPADS failed to influence ileum contractions to exogenous acetylcholine or histamine. It is concluded that, in addition to its direct contractile action in the guinea-pig ileum, ATP can activate (partly preganglionic) cholinergic neurones, an effect whose mechanism is largely different from that of alpha,beta-methylene ATP. ATP also causes relaxation by a direct, probably P2Y-receptor-mediated effect on the smooth muscle. All motor effects of ATP are inhibited by the antagonist PPADS.
    Basic &amp Clinical Pharmacology &amp Toxicology 06/2006; 98(5):488-95. · 2.12 Impact Factor
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    ABSTRACT: Moderate concentrations of the sensory stimulant drug capsaicin caused relaxation in human and animal intestinal circular muscle preparations (guinea-pig proximal, mouse distal colon, human small intestine and appendix) in vitro. With the exception of the guinea-pig colon, the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine (L-NOARG; 10(-4) M) strongly inhibited the relaxant effect of capsaicin. Tetrodotoxin, an inhibitor of voltage-sensitive Na+ channels failed to significantly reduce the inhibitory effect of capsaicin in the guinea-pig colon, human ileum and appendix; it caused an approximately 50% reduction in the mouse colon. The relaxant effect of capsaicin was strongly reduced in colonic preparations from transient receptor potential vanilloid type (TRPV1) receptor knockout mice as compared to their wildtype controls. It is concluded that nitric oxide, possibly of sensory origin, is involved in the relaxant action of capsaicin in the circular muscle of the mouse and human intestine.
    Life Sciences 05/2005; 76(24):2773-82. · 2.56 Impact Factor
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    ABSTRACT: Studying the visceral effects of the sensory stimulant capsaicin is a useful and relatively simple tool of neurotransmitter identification and has been used for this purpose for approximately 25 years in the authors' and other laboratories. We believe that conclusions drawn from experiments on visceral preparations may have an impact on studies dealing with the central endings of primary afferent neurons, i.e. research on nociception at the spinal level. The present review concentrates on the effects of capsaicin--through the transient receptor potential vanilloid receptor type 1 (TRPV1) receptor--on innervated gastrointestinal, respiratory and genitourinary smooth muscle preparations. Tachykinins and calcitonin gene-related peptide (CGRP) are the most widely accepted transmitters to mediate "local efferent" effects of capsaicin-sensitive nerves in tissues taken from animals. Studies more and more frequently indicate a supra-additive interaction of various types of tachykinin receptors (tachykinin NK(1), NK(2), NK(3) receptors) in the excitatory effects of capsaicin. There is also evidence for a mediating role of ATP, acting on P(2) purinoceptors. Non-specific inhibitory actions of capsaicin-like drugs have to be taken into consideration while designing experiments with these drugs. Results obtained on human tissues may be sharply different from those of animal preparations. Capsaicin potently inhibits tone and movements of human intestinal preparations, an effect mediated by nitric oxide (NO) and/or vasoactive intestinal polypeptide.
    European Journal of Pharmacology 11/2004; 500(1-3):143-57. · 2.59 Impact Factor
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    ABSTRACT: An attempt has been made to pharmacologically isolate cholinergic, P(2) purinoceptor-mediated and peptidergic (capsaicin-sensitive, tachykinin-mediated) contraction of the guanethidine-treated rat bladder detrusor preparation, in vitro. The effect of experimental diabetes was assessed on these types of contraction. Responses were evoked by electrical field stimulation (single shocks or 1 Hz for 30 s or 10 Hz for 40 s). Single shocks and 1-Hz stimulation were applied in the presence of (a). atropine (1 microM) or (b). P(2) purinoceptor antagonists (50 microM pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) [PPADS] plus 100 microM suramin. Long-term electrical field stimulation (10 Hz for 40 s) (c). was applied with both atropine and the P(2) purinoceptor antagonists present in the organ bath. The effects of capsaicin (d). and ATP (e). were also studied. Three groups of experimental animals were used: streptozotocin-treated (50 mg.kg(-1) i.p., 8 weeks before the experiment), parallel solvent-treated and untreated rats. (a). Responses to electrical field stimulation in the presence of atropine were reduced by half by PPADS plus suramin, but were resistant to capsaicin tachyphylaxis. They were enhanced in preparations taken from diabetic rats. (b). Contractions to electrical field stimulation in the presence of PPADS plus suramin were reduced by 2/3 by atropine, but were left unchanged by capsaicin or diabetes. (c). Contractions to long-term stimulation had a quick and a sustained phase. Especially the latter was inhibited by capsaicin tachypyhlaxis; it was also strongly reduced in preparations taken from diabetic rats. (d). Contractions to capsaicin (30 nM and 1 microM) were resistant to tetrodotoxin, strongly reduced by a combination of tachykinin NK(1) and NK(2) receptor antagonists, and slightly reduced in preparations from diabetic animals. Capsaicin (1 microM) had no acute inhibitory action on cholinergic or purinergic responses, nor did it cause relaxation in precontracted preparations treated with tachykinin receptor antagonists. (e) ATP-induced contractions were strongly reduced by PPADS plus suramin (50 plus 100 microM) and to a similar degree by 100 plus 200 microM, respectively. It is concluded that experimental diabetes selectively impairs peptidergic, capsaicin-sensitive responses (especially those that involve impulse conduction) in the rat detrusor preparation. The contractile response to electrical field stimulation that remains after atropine plus the P(2) purinoceptor antagonists has a yet unknown transmitter background.
    European Journal of Pharmacology 10/2003; 478(1):73-80. · 2.59 Impact Factor
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    ABSTRACT: Repeated experiments to localise serotonin in the myenteric plexus of rabbit ileum failed. After preincubation in serotonin (10(-5) M), an extensive varicose fibre system was detected by immunocytochemical methods. Stained fibres left the myenteric plexus and ran to the muscle layers. Labelled cell bodies could not be found, even after pretreatment with colchicine or pargyline. Application of reserpine (10(-5) M) and fluoxetine (10(-5) M) prevented serotonin uptake. Antisera against tryptophan hydroxylase revealed a rich fibre system, including those processes that entered the tertiary plexus. These fibres were able to accumulate serotonin, but again the cell bodies could not be detected. Serotonin caused concentration-dependent contraction in the longitudinal muscle layer of the rabbit ileum. Pretreatment with tetrodotoxin strongly reduced the effect of serotonin. Preapplication of atropine caused a slight decrease of response evoked by serotonin. Combined administration of tetrodotoxin and atropine significantly reduced the responses to serotonin, but did not abolish them. At the same time, agonists of 5-HT(2) and 5-HT(4) receptors caused concentration-dependent contractions. Our studies show that: 1). Without pretreatment, serotonin cannot be detected in the myenteric plexus of rabbit ileum. 2). An extensive uptake system works in this plexus. If released from myenteric nerve fibres, serotonin may evoke contractions in indirect and direct ways. 3). There may be an extrinsic serotoninergic innervation from the mesenteric ganglia. 4). Serotonin exerts its effect through 5-HT(2) and 5-HT(4) receptors on smooth muscle cells and nerve elements.
    The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 05/2003; 271(2):368-76.
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    ABSTRACT: The relaxant effect of capsaicin (300 nM) has been studied on mucosa-free circular strips of the human sigmoid colon in vitro. The response of precontracted preparations to capsaicin (sub-maximal relaxation) was reduced by over 50% by the nitric oxide synthase inhibitor N(G)-nitro- L-arginine (L-NOARG; 20 microM or 100 microM) or by the guanylate cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), but not by tetrodotoxin (1 microM) or the P(2) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS; 50 microM). L-NOARG or ODQ caused moderate contraction of the circular muscle, indicating a tonic "nitrergic" control. Anandamide (1-100 microM), an endogenous cannabinoid and capsaicin VR(1) receptor stimulant, failed to either mimic or modify the response to capsaicin (300 nM). It is proposed that capsaicin causes the release of smooth muscle relaxant substance(s) from afferent nerve endings in the gut wall, in a tetrodotoxin-resistant manner. Nitric oxide (possibly released from capsaicin-sensitive afferents) plays an important role in the capsaicin-evoked response. No evidence has been found for an involvement of PPADS-sensitive P(2) purinoceptors in the response to capsaicin or for a stimulation or inhibition of capsaicin-sensitive receptors by anandamide in the human sigmoid colon.
    Archiv für Experimentelle Pathologie und Pharmakologie 12/2002; 366(5):496-500. · 2.15 Impact Factor
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    ABSTRACT: Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating peptide-(1-38) (PACAP) have been found to stimulate distension-induced peristaltic motility in the guinea-pig isolated small intestine. In this study, we tested whether the putative VIP/PACAP receptor antagonist PACAP-(6-38) counteracts the properistaltic effect of VIP and PACAP in isolated segments of the guinea-pig small intestine. VIP (100 nM) and PACAP (30 nM) had a stimulatory effect, i.e., lowered the peristaltic pressure threshold at which peristaltic waves were triggered and enhanced the frequency of peristaltic waves. PACAP-(6-38) (3 microM) was per se without effect on peristalsis but prevented or reversed the peristaltic motor stimulation caused by VIP, when it was given before or after the agonist, respectively. PACAP-(6-38), however, failed to antagonize the properistaltic effect of PACAP. In ileal circular strips treated with tetrodotoxin (1 microM) and indomethacin (3 microM), spontaneous myogenic activity was inhibited by VIP (5-30 nM). This effect was significantly reduced by a pretreatment with PACAP-(6-38) (3 microM). A similar inhibition by PACAP-(1-38) (10-500 nM) was not influenced by the antagonist. It is concluded that PACAP-(6-38) is a VIP receptor antagonist, both in the peristaltic motor pathways and at the level of the circular muscle of the guinea-pig small intestine. The lack of a motor effect of PACAP-(6-38) on its own indicates that VIP acting on PACAP-(6-38)-sensitive receptors (located on neurons and/or the smooth muscle) is unlikely to participate in peristaltic motor regulation.
    European Journal of Pharmacology 12/2001; 431(2):259-64. · 2.59 Impact Factor
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    ABSTRACT: The chemical neuroanatomy of the stomatogastric nervous system of the earthworm, Eisenia fetida, has been investigated, using antibodies raised against serotonin, tyrosine hydroxylase, octopamine, GABA, FMRFamide, proctolin, Eisenia tetradecapeptide and neuropeptide Y. Neurons immunoreactive to these antibodies can be observed in the stomatogastric ganglia. The labelled cells comprise altogether 95.4% of the total number of neurons in the ganglion. Immunoreactive projections were followed between stomatogastric individual ganglia as well as towards the enteric plexus. Intrinsic neurons containing the different signal molecules examined are present along the entire length of the enteric plexus, but serotonin immunoreactive perikarya were only found in the hindgut. The density of the different immunoreactive neurons, except the serotonin ones, is highest in the pharyngeal plexus, and the number of labelled neurons decreases along the alimentary canal towards the hindgut. A number of epithelial cells also reveal tyrosine hydroxylase, octopamine, GABA and Eisenia tetradecapeptide immunoreactivity. The action of some putative neurotransmitters, such as dopamine, octopamine, serotonin and proctolin was tested on foregut preparations. Dopamine and octopamine (10(-6)-10(-4) M) have an excitatory effect on the musculature, whereas the effect of serotonin depends on the actual muscle tension. Following precontraction evoked by acetylcholine, serotonin in low concentrations (10(-7)-10(-6) M) causes relaxation, whereas in higher (10(-4) M) concentration it evokes slight contractions. In preparations at basal tone, serotonin (10(-7)-10(-6) M) evokes contractions of the foregut. Atropine strongly inhibits the action of acetylcholine but is ineffective against serotonin, dopamine and octopamine. Similarly, the Na+ channel blocker tetrodotoxin fails to influence the contractile effect of dopamine, octopamine and serotonin. These results suggest that dopamine, octopamine and serotonin act directly on the muscle cells of the alimentary tract. Proctolin do not evoke any significant effect on the foregut.
    Journal of Neurocytology 05/2001; 30(4):313-25. · 1.94 Impact Factor
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    ABSTRACT: The effects of the P(2)-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl- 2('),4(')- disulphonic acid (PPADS), the nitric oxide (NO) synthase inhibitor N(G)-nitro- l -arginine (l -NOARG), the K(+)-channel blocker apamin, the pituitary adenylate cyclase activating peptide (PACAP) antagonist PACAP(6-38) and the sensory neuron-blocking drug capsaicin were examined on the non-adrenergic, non-cholinergic (NANC) relaxation evoked by electrical field stimulation in the longitudinal muscle of the guinea-pig proximal colon. Both PPADS (50 microm) and l -NOARG (100 microm) significantly inhibited the NANC relaxation. In the presence of l -NOARG, PPADS inhibited and apamin (100 nm) practically abolished the response. Capsaicin slightly but significantly enhanced the NANC relaxation at 10, but not at 1 Hz stimulation frequency. PACAP(6-38) (3 microm) had no effect on the NANC relaxation, although it abolished the relaxant effect of exogenous PACAP(1-27) (10 nm) and reduced that of exogenous vasoactive intestinal polypeptide (VIP, 30-100 nm) by about 60 %. PPADS (50 microm) inhibited the relaxant action of exogenous adenosine 5(')-triphosphate (ATP; 1 and 10 microm), the inhibition being stronger at 1 microm ATP. These data indicate that an exogenous P(2)-purinoceptor stimulant (possibly ATP) and NO are involved in the NANC relaxation of the guinea-pig colon. The 'non-nitrergic' apamin-sensitive component of the response might also include an unidentified transmitter. No evidence has been found for a mediating role of PACAP/VIP-like peptides.
    Pharmacological Research 02/2001; 43(1):83-7. · 4.35 Impact Factor
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    ABSTRACT: The contractile effect of capsaicin in the guinea-pig small intestine involves an activation of enteric cholinergic neurons. Our present data show that the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, 30 μM) significantly reduces the contractile response to capsaicin (2 μM) in the presence, but not in the absence, of the tachykinin receptor antagonists [O-Pro9, (Spiro-γ-lactam)Leu10, Trp11]physalaemin (1–11) (GR 82334; 3 μM) and (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl)propyl)-4-phenylpiperidine-4-yl)-N-methylacetamide (SR 142801; 100 nM) (for blocking tachykinin NK1 and NK3 receptors, respectively). PPADS (30 μM) fails to influence submaximal cholinergic contractions evoked by cholecystokinin octapeptide (CCK-8; 2–3 nM) or senktide (1 nM), or the direct smooth muscle-contracting effect of histamine (100–200 nM). A higher concentration (300 μM) of PPADS is also without effect against the stimulatory action of cholecystokinin octapeptide. This means that PPADS can probably be safely used as a purinoceptor antagonist in intestinal preparations. The putative pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist PACAP-(6–38) (3 μM) significantly reduces the contractile effect of PACAP-(1–38) (10 nM) and abolishes that of vasoactive intestinal polypeptide (VIP; 10 nM). PACAP-(6–38) (3 μM) fails to influence the effect of capsaicin (2 μM) both in the absence and in the presence of tachykinin receptor antagonists. The nitric oxide (NO) synthase inhibitor NG-nitro-l-arginine (l-NOARG; 100 μM) also fails to inhibit the capsaicin-induced motor response. We conclude that an endogenous ligand of PPADS-sensitive P2 purinoceptors (possibly ATP), but not a VIP/PACAP-like peptide or NO, is involved in the nontachykininergic activation of cholinergic neurons in the course of the capsaicin-induced contraction.
    European Journal of Pharmacology 04/2000; · 2.59 Impact Factor
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    ABSTRACT: The effect of the pituitary adenylate cyclase activating polypeptide (PACAP) receptor antagonist PACAP(6-38) on the relaxant response to exogenous PACAP, vasoactive intestinal polypeptide (VIP) and non-adrenergic, non-cholinergic (NANC) nerve stimulation was tested in the guinea-pig taenia caeci, in the presence of atropine (10-6 M) and guanethidine (3&#5010-6 M). PACAP(6-38) (3&#5010-6 M) strongly inhibited sub-maximal relaxations evoked by exogenous PACAP (1-3&#5010-8 M) or VIP (10-8 M), but not those due to isoprenaline (4-8&#5010-8 M) or ATP (10-6 M). PACAP(6-38) caused a small but significant (approximately 20%) inhibition of the NANC relaxation due to electrical field stimulation (1 Hz or 10 Hz for 20 s). At these frequencies PACAP(6-38) caused no inhibition of the NANC relaxation in the presence of the P2 purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5&#5010-5 M), or PPADS plus the NO-synthase blocker NG-nitro-l-arginine (l-NOARG; 10-4 M); in preparations pretreated with l-NOARG (10-4 M) alone PACAP(6-38) retained its inhibitory effect. The PPADS- and l-NOARG-resistant NANC relaxation with 10 Hz electrical stimulation was blocked by apamin (10-7 M); it was not significantly modified by the tachykinin receptor antagonist spantide (10-5 M). Tachyphylaxis to PACAP(1-27) (10-7 M for 10 min) strongly inhibited the relaxation due to PACAP(1-38) (1-3&#5010-8 M) and reduced electrical stimulation-evoked relaxations by half. The putative VIP antagonist VIP(10-28) (10-5 M) failed to significantly reduce the relaxant action of exogenous VIP (1-3&#5010-8 M). Relaxation induced by PACAP(1-38) (1-2&#5010-8 M) was not influenced by a mixture of PPADS (5&#5010-5 M) and l-NOARG (10-4 M). It is concluded that: (a) PACAP(6-38) is a VIP/PACAP antagonist in the guinea-pig taenia caeci; (b) a release of a VIP/PACAP-like substance from enteric nerves is involved in the NANC relaxation in this preparation, but its contribution is relatively small and seems to depend on the functional integrity of the PPADS-sensitive inhibitory mechanism; (c) the PPADS- plus l-NOARG-resistant NANC relaxation probably involves apamin-sensitive K+ channels.
    Archiv für Experimentelle Pathologie und Pharmakologie 01/2000; 361(5):492-497. · 2.15 Impact Factor
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    ABSTRACT: Relations between P2 purinoceptors and capsaicin-sensitive sensory neurons include an excitatory action of P2 purinoceptor agonists on spinal afferent neurons, as well as release of ATP from afferents at their central and peripheral endings, and a possible participation of ATP in nociception and/or in 'local efferent' responses mediated by sensory nerves at the periphery. The present paper briefly summarizes available evidence on these interrelations. Ample evidence shows that ATP and other P2 purinoceptor agonists can activate primary afferent neurons, through P2X3 receptors and probably other purinoceptors as well, but evidence for an involvement of P2 purinoceptors in nociception or in 'local efferent' responses due to activation of primary afferents is, at best, circumstantial. The possibility is also dealt with that P2 purinoceptor activation may cause small intestinal contraction with the mediation of capsaicin-sensitive sensory neurons and that the motor response to capsaicin in this tissue may involve the release of a P2 purinoceptor stimulant from sensory nerves. Our data show that cholinergic contractions of the guinea-pig ileum in response to the P2 purinoceptor agonist alpha,beta-methylene ATP (alpha,beta-meATP) are blocked by atropine, but not by in vitro capsaicin pretreatment (which completely blocks the contractile action of capsaicin). Cholinergic ileum contractions due to capsaicin (2 microM) are insensitive to suramin (a P2 purinoceptor antagonist; 100 microM). In the presence of antagonists acting at tachykinin NK1 and NK2 receptors, however, suramin (100 microM) causes a significant inhibition of the capsaicin-evoked contraction. These data indicate that capsaicin-sensitive nerves are not involved in the excitatory effect of alpha,beta-methylene ATP on myenteric neurons. On the other hand, ATP is probably involved in the 'non-tachykininergic' component of the capsaicin-induced excitatory response of the small intestine. ATP may originate from sensory neurons and probably acts as activator of myenteric nerves.
    European Journal of Pharmacology 07/1999; 375(1-3):203-10. · 2.59 Impact Factor
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    ABSTRACT: A vállalt munka fő céljai: Izolált szervi kísérletekben megismerni a zsigerek mozgásválaszainak mechanizmusait, az állatokon kapott eredményeket humán preparátumokkal összevetve. Szenzoros és más eredetű nem-adrenerg, nem-kolinerg (NANC) transzmitterek azonosítása (funkcionális vizsgálatok és a transzmitter-felszabadulás mérése). Kóros zsigeri működések modellezése. (Egyes irányokban komplett, másokban tájékozódó kísérletek). Közölt eredmények: Új humán adatok közlése mellett összefoglaltuk a kapszaicin zsigeri hatásaival, transzmittereivel kapcsolatos jelentősebb eredményeket. Alappal fölvetettük annak lehetőségét, hogy emberben?és bizonyos állatfajokban is?az NO szenzoros transzmitter (Barthó et al. 2004?Eur J Pharmac; Benkó et al. 2005?Life Sci). Mind állati, mind (világelsőként) humán GI preparátumokban bizonyítottuk az ATP közvetítő szerepét NANC válaszokban (Undi et al. 2005?Bas Clin Pharmac; 2006?Brain Res Bull; Benkó et al 2006?NS Arch Pharmac, 2007?Neurosci). Nem találtunk bizonyítékot VIP szerepére emberi bél kapszaicinnel kiváltott gátló válaszában, a CO szerepére perisztaltikus reflexben (kongresszusi közlés), ill a CO szerepére a NANC gátló válaszban állati és humán GI preparátumokon (ld. fenti közlemények). Közlésre vár: P-anyag és CGRP-IR felszabadulás bélből; szenzoros izgató mustárolaj és H2S hatásmechanizmusa; a passzív szenzibilizáció/antigén-expozíció hatásainak elemzése állati és emberi GI és légúti simaizomzaton stb. | Aims of the project Experiments on isolated tissues for elucidating the mechanisms behind some evoked movements of viscera of animals and man. Identifying sensory and other non-adrenergic, non-cholinergic (NANC) transmitters. Measuring neurotransmitter release. Modelling pathophysiological processes of viscera. (Planned were complete series of experiments in some and pilot experiments in other directions.) Published results Review, containing original results, on visceral effects of capsaicin and the transmitters thereof. Providing indirect evidence that NO is a sensory neurotransmitter (Bartho et al. 2004?Eur J Pharmac; Benko et al. 2005?Life Sci). Proving the presence of purinergic innervation of human (Undi et al. 2006?Brain Res Bull; Benko et al. 2007?Neurosci) and rat intestine (Benko et al. 2006?NS Arch Pharmac). No evidence for a mediating role of VIP in the inhibitory effect of capsaicin in the human gut, a role of CO in the peristaltic reflex (congress presentations) or in the evoked NANC relaxation in animal or human GI preparations (papers as above). To be published Release of substance P- or CGRP-like IR from the gut; mechanisms of action of the sensory stimulants mustard oil and H2S; effects of passive sensitization/antigen exposure on GI and respiratory smooth muscles of animals and man, etc.