title: Vasoactive intestinal peptide (VIP) as transmitter of inhibitory motor neurons of the gut: evidence from the use of selective VIP antagonists and VIP antiserum.
abstract: The role of vasoactive intestinal peptide (VIP) in neurally mediated relaxation of guinea pig and rat intestine was examined with three putative VIP antagonists: a C-terminal sequence of VIP (VIP10-28), substituted analogs of VIP ([4-Cl-D-Phe6, Leu17]VIP) and growth hormone releasing factor (GRF) ([Ac-Tyr1, D-Phe2] GRF1-29). The three agents inhibited selectively relaxation induced by VIP and its homolog, peptide histidine isoleucine. Inhibition of VIP-induced relaxation in tenia coli and gastric fundic strips was consistent with competitive antagonism. Relaxation induced by field stimulation (80 V; 1 msec; 0.1-16 Hz) which is accompanied by a stoichiometric increase in VIP release was inhibited by the three antagonists in the following order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The descending relaxation component of the peristaltic reflex induced by graded stretch of the orad end of a rat colonic segment which is also accompanied by an increase in VIP release, was inhibited by the three VIP antagonists in the same order of potency: VIP10-28 greater than VIP analog greater than GRF analog. The most potent antagonist, VIP10-28, abolished descending relaxation at the lowest grades of stretch (2 and 4 g) and inhibited relaxation at the highest grades of stretch (10 g) by 79%. The results indicate that VIP (and peptide histidine isoleucine) is the transmitter responsible for neurally induced gastric and intestinal relaxation.
authors.affiliation: Department of Physiology and Medicine, Medical College of Virginia, Richmond.
authors.forename: J R
authors.initials: JR
authors.lastname: Grider
authors.forename: J R
authors.initials: JR
authors.lastname: Rivier
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D013007:Growth Hormone-Releasing Hormone; C059148:somatotropin releasing hormone (1-29)