Carbachol does not down-regulate substance P receptors in pancreatic acini.
In a previous study, we found that first incubating guinea pig pancreatic acini with carbachol caused desensitization of the enzyme secretory response to cholecystokinin-octapeptide (CCK-8), bombesin, and carbachol but not that to substance P. This carbachol-induced desensitization could be accounted for by carbachol-induced down-regulation of receptors for CCK-8, bombesin, and carbachol. Although carbachol did not desensitize the enzyme secretory response to substance P, an effect of carbachol on substance P receptors was not examined. In the present study, in dispersed acini from guinea pig pancreas, substance P caused a twofold increase in amylase secretion. Stimulation was half-maximal at 0.7 nM and was maximal at 10 nM. Analysis of the ability of substance P to inhibit binding of 125I-substance P to substance P receptors indicated that acini possess a single class of receptors for substance P (Kd = 0.8 +/- 0.1 nM; Bmax = 1,037 +/- 145 fmol/mg of DNA). There was a close correlation between the relative potency with which substance P stimulated amylase secretion (0.7 nM) and the potency for inhibiting binding of 125I-substance P (Kd = 0.8 nM). First incubating pancreatic acini with carbachol did not alter either substance P-stimulated enzyme secretion or binding of 125I-substance P to substance P receptors, whereas in the same experiments, carbachol reduced binding of 125I-CCK-8 to cholecystokinin receptors by 50% and decreased in CCK-8-stimulated enzyme secretion by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
Patto
R J
RJ
Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
Vinayek
R
R
Jensen
R T
RT
Gardner
J D
JD
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D007457:Iodine Radioisotopes; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000502:physiology / Q000648:ultrastructure*; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism
D007457:Iodine Radioisotopes; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D002217:Carbachol; D000681:Amylases; D012844:Sincalide; D001839:Bombesin