Inhibition of VIP-stimulated ion transport by a novel Y-receptor phenotype in rabbit distal colon.
Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut.
G H
GH
Ballantyne
J R
JR
Goldenring
F X
FX
Fleming
S
S
Rush
J S
JS
Flint
L P
LP
Fielding
H J
HJ
Binder
I M
IM
Modlin
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity / Q000187:drug effects; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009478:Neuropeptide Y / Q000494:pharmacology*; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002712:Chlorides; D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D014660:Vasoactive Intestinal Peptide; D010191:Pancreatic Polypeptide; D012964:Sodium; D000242:Cyclic AMP