Effect of VIP and PACAP on basal release of serotonin from isolated vascularly and luminally perfused rat duodenum.
The effect of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), and PACAP-27 on the release of serotonin (5-HT) into the intestinal lumen and the portal circulation was studied by using in vivo isolated vascularly and luminally perfused rat duodenum. 5-HT levels were determined by HPLC. VIP, PACAP-38, and PACAP-27 reduced the luminal release of 5-HT but did not affect the vascular release of 5-HT. The inhibitory effect caused by VIP, PACAP-38, and PACAP-27 was not affected by either atropine, hexamethonium, TTX, or TTX plus ACh, but it was completely antagonized by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA). The VIP receptor antagonist VIP-(10-28) blocked the effects of VIP, PACAP-38, and PACAP-27. These results suggest that VIP and PACAP exert a direct inhibitory effect on the luminal release of 5-HT from the enterochromaffin (EC) cells via a common receptor site on the EC cells and that this effect is mediated by NO but not by cholinergic pathways. A single injection of TTX, atropine, or hexamethonium reduced the luminal release of 5-HT, whereas a single injection of VIP-(10-28) stimulated the luminal release of 5-HT and this effect was antagonized by atropine, hexamethonium, or TTX. These results suggest that EC cells may receive the direct innervation of cholinergic neurons as well as VIP and/or PACAP neurons, with the former exerting a tonic stimulatory influence and the latter exerting a tonic inhibitory influence on 5-HT release into the intestinal lumen.
Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga 520-21, Japan.
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M
Fujimiya
H
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Yamamoto
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A
Kuwahara
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004386:Duodenum / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D018738:Hexamethonium / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013552:Swine; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology* / Q000502:physiology
C495401:ADCYAP1 protein, human; C495403:Adcyap1 protein, rat; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D019335:Nitroarginine; D012701:Serotonin; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D013779:Tetrodotoxin; C047945:vasoactive intestinal peptide (10-28); D001285:Atropine; D001120:Arginine; D000109:Acetylcholine