Presynaptic modulation of cholinergic neurotransmission in the human proximal stomach.
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.
Leclere
Pascal G
PG
Heymans Institute of Pharmacology, Ghent University, Faculty of Medicine and Health Sciences, De Pintelaan 185, B-9000 Ghent, Belgium.
Lefebvre
Romain A
RA
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
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