Regional difference in correlation of 5-HT4 receptor distribution with cholinergic transmission in the guinea pig stomach.
Localization and function of 5-HT4 receptors in the stomach were examined in mucosa-free preparations of antrum, corpus and fundus from guinea pig stomach by determination of acetylcholine release and in vitro receptor autoradiography. Specific [125I]SB207710, (1-n-butyl-4-piperidinyl) methyl-8-amino-7-iodo-1,4-benzodioxane-5-carboxylate, binding sites were detected in 3 regions of the stomach. High densities of binding were observed in the myenteric plexus of antrum and corpus, but not fundus. In mucosa-free preparations treated with 5-HT1, 5-HT2 and 5-HT3 receptor antagonists, 5-HT (10(-8)-10(-6) M) potentiated the electrically stimulated (0.5 Hz, 1 ms) outflow of [3H]acetylcholine from antrum and corpus strips preloaded with [3H]choline, but not from fundus strips, and the potentiation was antagonized by SB204070, (1-n-butyl-4-piperidinyl) methyl-8-amino-7-chloro-1,4-benzodioxane-5-carboxylate. Thus, 5-HT4 receptors are located on myenteric cholinergic neurons in the antrum and corpus of guinea pig stomach and their activation evokes the release of acetylcholine.
Takada
K
K
Department of Pharmacology, Nagasaki University School of Medicine, Japan.
Sakurai-Yamashita
Y
Y
Yamashita
K
K
Kaibara
M
M
Hamada
Y
Y
Nakane
Y
Y
Hioki
K
K
Taniyama
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001667:Binding, Competitive; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000294:innervation; D009435:Synaptic Transmission
D004146:Dioxanes; D007457:Iodine Radioisotopes; D010880:Piperidines; D011985:Receptors, Serotonin; C088873:SB 207710; D012702:Serotonin Antagonists; C084858:SB 204070A; D044422:Receptors, Serotonin, 5-HT4; D012701:Serotonin; D000109:Acetylcholine