Y2 receptors for peptide YY and neuropeptide Y on dispersed chief cells from guinea pig stomach.
Peptide YY (PYY) and neuropeptide Y (NPY) inhibit agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production and pepsinogen secretion from chief cells. We used radiolabeled PYY and NPY to characterize receptors on chief cells from guinea pig stomach. Binding of 125I-labeled PYY was rapid (70% maximal within 10 min) and specific (not inhibited by secretin, vasoactive intestinal peptide, cholecystokinin, carbachol, prostaglandin E2, forskolin, or cholera toxin). Measurement of the ability of PYY to inhibit binding of 125I-PYY indicated the presence of 1.8 x 10(3) high-affinity [dissociation constant (Kd) = 1.7 nM] and 5.1 x 10(4) low-affinity (Kd = 83.3 nM) sites/cell. Internalization of bound 125I-PYY was suggested by slow and incomplete dissociation in the presence of unlabeled PYY (50% after 2 h) and was examined further by measuring residual binding after washing with acetic acid (pH 2.5), glycine (pH 10.5), or trypsin. After 30 min at 37 degrees C, internalization of radioligand was evidenced by the failure of washing with these solutions to remove 50-65% of bound radioactivity. At 4 degrees C, internalization of 125I-PYY was nearly abolished. Binding of 125I-PYY and 125I-NPY was inhibited by NPY-(13-36) but not by [Leu31,Pro34]NPY indicating that these are Y2 receptors. In guinea pig chief cells, PYY and NPY modulate cAMP-mediated pepsinogen secretion by interacting with specific high-affinity Y2 receptors.
Singh
G
G
Department of Medicine, State University of New York-Health Science Center, Brooklyn 11203-2098.
Singh
L
L
Raufman
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D006168:Guinea Pigs; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D019894:Peptide YY; D010455:Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013270:Stomach / Q000166:cytology; D013696:Temperature; D013997:Time Factors
D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D019894:Peptide YY