Actions of peptide YY and neuropeptide Y on chief cells from guinea pig stomach.
Peptide YY (PYY), found in intestinal endocrine cells, and neuropeptide Y (NPY), a structural analogue of PYY found in neurons, inhibit gastric, pancreatic, and intestinal fluid and electrolyte secretion. We examined the effects of these peptides on dispersed chief cells from guinea pig stomach. PYY and NPY, but not pancreatic polypeptide, starting at nanomolar concentrations, caused a 40-50% inhibition of secretin-, vasoactive intestinal polypeptide-, prostaglandin E2-, and forskolin-induced increases in chief cell adenosine 3',5'-cyclic monophosphate (cAMP) content and pepsinogen secretion. These inhibitory peptides did not alter pepsinogen secretion caused by cholecystokinin, carbamylcholine, A23187, 8-bromo-cAMP, or a phorbol ester. The inhibitory effects of PYY on chief cell cAMP production occurred within 30 s, were independent of phosphodiesterase activity, and did not affect the actions of cholera toxin. However, the inhibitory effects of PYY were abolished when chief cells were preincubated with pertussis toxin, an agent that uncouples inhibitory guanine nucleotide binding (G) proteins from their receptors. In gastric chief cells, PYY and NPY attenuate the stimulatory effects of secretagogues whose actions are mediated by changes in cellular levels of cAMP. PYY-induced attenuation of chief cell adenylate cyclase activity appears to involve activation of inhibitory G proteins.
Raufman
J P
JP
Department of Medicine, State University of New York-Health Science Center, Brooklyn 11203-2098.
Singh
L
L
D037361:Adenylate Cyclase Toxin; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010435:Pepsinogens / Q000378:metabolism*; D019894:Peptide YY; D010455:Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide; D012633:Secretin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010435:Pepsinogens; D010455:Peptides; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D010566:Virulence Factors, Bordetella; D019894:Peptide YY; D012633:Secretin; D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol; D002772:Cholera Toxin; D037342:Pertussis Toxin; D015232:Dinoprostone; D012844:Sincalide