Short-term cholinergic desensitization of rat pancreatic secretory response.
Dispersed pancreatic acini were first exposed to carbamylcholine (10(-7)-10(-4) M) for 60 min, washed, and reexposed to this same agonist (10(-8)-10(-3) M) for 15 min. During this second incubation, the functional secretory capacity of these acini was evaluated by measuring amylase release. Acini preexposed to concentrations of carbamylcholine of 10(-6) M or greater showed shifts to the right in the subsequent carbamylcholine dose-response curves of amylase release. A 3-h recovery period (without carbamylcholine) did not restore the altered carbamylcholine dose-response curve. Ca2+ concentrations of 10(-7) M or 2.5 X 10(-3) M instead of 0.5 X 10(-3) M during the 60-min preincubation did not affect the desensitization process. With use of N-[3H]methylscopolamine to evaluate muscarinic receptors, the only changes observed after desensitization were a significant decrease in the high-affinity and an equivalent increase in that of the low-affinity receptors. After cholinergic exposure amylase release stimulated by caerulein was only slightly modified, whereas amylase release in response to a phorbol ester 12-O-tetradecanoylphorbol-13-acetate and to the ionophore A23187 was not altered. These data indicate that short-term desensitization with a cholinergic agent is relatively specific to muscarinic agonists, causes changes in the muscarinic receptor high- and low-affinity concentration but does not alter intracellular steps after calcium mobilization or protein kinase C activation known to be involved in the secretion process.
D000681:Amylases / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002217:Carbachol / Q000494:pharmacology*; D002108:Ceruletide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D019832:N-Methylscopolamine; D010179:Pancreas / Q000187:drug effects*; D010189:Pancreatic Juice / Q000378:metabolism*; D051381:Rats; D012602:Scopolamine Derivatives / Q000494:pharmacology; D012636:Secretory Rate / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D012602:Scopolamine Derivatives; D000001:Calcimycin; D002108:Ceruletide; D002217:Carbachol; D000681:Amylases; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D019832:N-Methylscopolamine