Carbachol-induced down-regulation of high-affinity receptors for vasoactive intestinal peptide.
When dispersed acini from guinea pig pancreas are first incubated with carbachol, the subsequent binding of 125I-vasoactive intestinal peptide (VIP) is inhibited during a second incubation. This inhibitory action of carbachol on binding of 125I-VIP depends on time, temperature, and the concentration of carbachol in the first incubation and can be blocked by atropine. First incubating acini with A23187, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), cholecystokinin octapeptide, bombesin, or 12-O-tetradecanoylphorbol-13-acetate does not alter binding of 125I-VIP. Adding EGTA to the first incubation medium abolishes the effect of carbachol on binding of 125I-VIP. In control acini or acini first incubated with carbachol, approximately half of the bound 125I-VIP can be stripped by acetic acid. 125I-VIP interacts with two distinct classes of receptors on pancreatic acini. One has a high affinity for VIP (Kd, 1 nM); the other has a low affinity for VIP (Kd, 2 microM). First incubating acini with carbachol decreases the number but not the affinity of high-affinity VIP receptors with no change in the number or affinity of low-affinity VIP receptors. Pancreatic acini possess two classes of muscarinic cholinergic receptors: one has a high affinity (Kd, 4 microM) and the other has a low affinity (Kd, 698 microM) for carbachol. The dose-response curve for carbachol-induced inhibition of binding of 125I-VIP and that for occupation of low-affinity muscarinic cholinergic receptors by carbachol are similar.(ABSTRACT TRUNCATED AT 250 WORDS)
Murakami
M
M
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Vinayek
R
R
Jensen
R T
RT
Gardner
J D
JD
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D011949:Receptors, Cholecystokinin; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D002217:Carbachol