AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 3 392-G397, Copyright © 1987 by American Physiological Society
Short-term cholinergic desensitization of rat pancreatic secretory response
J. Asselin, L. Larose and J. Morisset
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.
