AJP - Gastrointestinal and Liver Physiology, Vol 243, Issue 4 285-G290, Copyright © 1982 by American Physiological Society
Protein synthesis inhibitors enhance secretagogue sensitivity of in vitro rat pancreatic acini
M. Otsuki and J. A. Williams
Isolated rat pancreatic acini were treated with cycloheximide and amylase
release was measured. This agent increased the sensitivity to both
synthetic octapeptide of cholecystokinin (CCK8) and carbamylcholine, the
major secretagogues known to utilize Ca2+ as a second messenger. The
mechanism of the cycloheximide effect was via inhibition of protein
synthesis, as indicated by the following: 1) the concentration of
cycloheximide used inhibited leucine incorporation by greater than 90%; 2)
this effect was not instantaneous but increased up to a 2-h pretreatment;
and 3) a similar effect was obtained with puromycin, a chemically different
inhibitor of protein synthesis. Cycloheximide acted on the steps by which
secretagogues mobilize cellular Ca2+ because the dose-response curve for
45Ca2+ efflux was shifted to the same extent as that for amylase release,
whereas the dose-response curve for amylase release induced by the Ca2+
ionophore A23187 was not altered. The results suggest, therefore, that a
rapidly turning-over protein present in pancreatic acinar cells exerts an
inhibitory influence on Ca2+ mobilization by secretagogues.
