Facilitation by endogenous acetylcholine and nitric oxide of luminal serotonin release from the guinea-pig colon.
The present study was designed to determine the influence of endogenous acetylcholine and nitric oxide (NO) on spontaneous luminal serotonin (5-hydroxytryptamine, 5-HT) release in the luminally perfused isolated guinea-pig proximal colon in vitro. 5-HT was determined by high-performance liquid chromatography with electro-chemical detection. The luminal outflow of 5-HT was significantly reduced by atropine (0.2 microM), hexamethonium (100 microM), the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 10 microM) and the NO-trapping agent 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO, 30 microM). Addition of excess L-arginine (300 microM) reversed the inhibitory effect of L-NNA on the 5-HT outflow. Physostigmine (1 microM) caused a great increase (atropine-sensitive) in 5-HT outflow. The enhancing action of physostigmine on 5-HT outflow was partially inhibited by L-NNA (100 microM) or carboxy-PTIO (30 microM), but was unaffected by the muscarinic M1 receptor antagonist pirenzepine (0.2 microM) or a muscarinic M3 receptor antagonist 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (0.2 microM). These results suggest that 5-HT release from luminally perfused proximal colon of the guinea pig is stimulated via a NO pathway and cholinergic pathways which utilize muscarinic synapses and nicotinic synapses. Further, an intrinsic cholinergic-NO link appears to play a role in the stimulation of luminal 5-HT release, which may reflect the release of 5-HT from entero-chromaffin cells.
Kojima
S
S
Department of Pharmacology, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Ikeda
M
M
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001565:Benzoates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010830:Physostigmine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*
D001565:Benzoates; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D019335:Nitroarginine; D009569:Nitric Oxide; D012701:Serotonin; D001285:Atropine; D001120:Arginine; D010830:Physostigmine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine