AJP - Gastrointestinal and Liver Physiology, Vol 244, Issue 6 623-G629, Copyright © 1983 by American Physiological Society
Effects of in vivo cholinergic stimulation of rat exocrine pancreas
G. Adler, G. Gerhards, J. Schick, G. Rohr and H. F. Kern
Peptide and cholinergic secretagogues both produce biphasic dose-response
curves for pancreatic enzyme secretion in vitro: supraoptimal doses result
in submaximal secretory responses. We compared the effects of maximal and
supramaximal doses of a cholinergic agent (carbachol) on rat exocrine
pancreas in vivo. In conscious rats, volume and enzyme output were measured
from the cannulated pancreatic duct during infusion of carbachol for 3 h.
Infusion of 5 X 10(-7) mol . kg-1 . h-1 carbachol caused optimal
stimulation, whereas a supraoptimal dose (5 X 10(-6) mol . kg-1 . h-1)
resulted in submaximal response. Similar results were achieved when
discharge of amylase and protein synthesis was determined in vitro after
carbachol in vivo. Supraoptimal doses of carbachol increased serum amylase
and enhanced acinar cell lysosomal activity in the Golgi area. The latter
appeared to induce fusion of zymogen granules, which resulted in
cytoplasmic vacuoles. The in vivo results corroborate in vitro findings of
a biphasic dose-response relationship for carbachol and demonstrate
destructive effects of supraoptimal concentrations on target cells.
