title: Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach.
abstract: 1. This study investigates whether the cholinergic neurones, innervating the human proximal stomach, can be modulated by nitric oxide (NO) or vasoactive intestinal polypeptide (VIP), or via presynaptic muscarinic, alpha(2)- or 5-hydroxytryptamine(4) (5-HT(4)-) receptors. 2. Circular muscle strips, without mucosa, were incubated with [(3)H]-choline to incorporate [(3)H]-acetylcholine into the cholinergic transmitter stores. The basal and electrically-induced release of tritium and [(3)H]-acetylcholine were analysed in a medium containing guanethidine (4 x 10(-6) M), hemicholinium-3 (10(-5) M), physostigmine (10(-5) M) and atropine (10(-6) M). Tissues were stimulated twice for 2 min (S(1) and S(2): 40 V, 1 ms, 4 Hz) and drugs were added before S(2). 3. The NO synthase inhibitor L-N(G)-nitroarginine methyl ester (3 x 10(-4) M) and the NO donor sodium nitroprusside (10(-5) M), as well as VIP (10(-7) M) did not influence the basal release nor the electrically-evoked release. 4. The alpha(2)-adrenoceptor agonist UK-14,304 (10(-5) M) significantly inhibited the electrically-evoked release of [(3)H]-acetylcholine, and this was prevented by the alpha(2)-adrenoceptor antagonist rauwolscine (2 x 10(-6) M). 5. The 5-HT(4)-receptor agonist prucalopride (3 x 10(-7) M) significantly enhanced the electrically-evoked release of [(3)H]-acetylcholine, and the 5-HT(4)-receptor antagonist SB204070 (10(-9) M) prevented this. 6. When atropine (10(-6) M) was omitted from the medium and added before the second stimulation, it significantly increased the release of [(3)H]-acetylcholine. 7. These results suggest that the release of acetylcholine from the cholinergic neurones, innervating the circular muscle in the human proximal stomach, can be inhibited via presynaptic muscarinic auto-receptors and alpha(2)-adrenoceptors, and stimulated via presynaptic 5-HT(4)-receptors. No evidence for modulation by NO or VIP was obtained.
authors.affiliation: Heymans Institute of Pharmacology, Ghent University, Faculty of Medicine and Health Sciences, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Pascal G
authors.initials: PG
authors.lastname: Leclere
authors.forename: Romain A
authors.initials: RA
authors.lastname: Lefebvre
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001285:Atropine / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D004146:Dioxanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects; D017661:Receptors, Presynaptic / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects; D044422:Receptors, Serotonin, 5-HT4; D018005:Receptors, Vasoactive Intestinal Peptide / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D001572:Benzofurans; D004146:Dioxanes; D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D018727:Muscarinic Antagonists; D020030:Nitric Oxide Donors; D010880:Piperidines; D011810:Quinoxalines; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D011985:Receptors, Serotonin; D018005:Receptors, Vasoactive Intestinal Peptide; D012702:Serotonin Antagonists; C406662:prucalopride; C084858:SB 204070A; D044422:Receptors, Serotonin, 5-HT4; D009599:Nitroprusside; D015016:Yohimbine; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D000068438:Brimonidine Tartrate; D001285:Atropine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester