Vasoactive intestinal peptide (VIP) as transmitter of inhibitory motor neurons of the gut: evidence from the use of selective VIP antagonists and VIP antiserum.
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.
Grider
J R
JR
Department of Physiology and Medicine, Medical College of Virginia, Richmond.
Rivier
J R
JR
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*
D010446:Peptide Fragments; D014660:Vasoactive Intestinal Peptide; C047945:vasoactive intestinal peptide (10-28); D013007:Growth Hormone-Releasing Hormone; C059148:somatotropin releasing hormone (1-29)