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1 Department of Anatomy,
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-(1028)
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.
luminal release; isolated perfusion; vasoactive intestinal polypeptide; pituitary adenylate cyclase-activating peptide
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