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In order to investigate the actions of acetylcholine and short-chain fatty acids on acinar cells of the exocrine pancreas of sheep, measurements of amylase release and 45Ca efflux from superfused segments, as well as changes in membrane potential, input resistance and equilibrium potential in the acinar cells, were carried out in vitro. The application of acetylcholine or short-chain fatty acids caused a dose-dependent increase in amylase release from the superfused tissue segments. The amylase release evoked by 10(-3) M-short-chain fatty acids containing 2-8 carbon atoms increased with increasing carbon number, up to 5 (i.e. it was maximum with iso-valerate, which has 5 carbon atoms). The amylase release stimulated by acetylcholine (5.5 X 10(-6) M) or caprylate (10(-3) was accompanied by an increase in 45Ca efflux, and was significantly reduced by the removal of extracellular Ca2+. The stimulating effect of caprylate (10(-3) M) on amylase secretion was also observed in superfused segments of the guinea-pig, but not in those of the mouse, rabbit or hamster. The resting membrane potential and input resistance of acinar cells of sheep pancreas were -31.1 +/- 1.6 mV and 2.7 +/- 0.7 M omega (means +/- S.E. of means), respectively. The application of acetylcholine or short-chain fatty acids always depolarized the cell membrane and reduced the input resistance. The effect of short-chain fatty acids was observed in the presence of atropine (1.4 X 10(-6) M). The equilibrium potentials for acetylcholine and butyrate were -15.0 +/- 0.8 and -16.0 +/- 1.1 mV, respectively. It is concluded that the cellular secretory process evoked by acetylcholine is qualitatively similar to that of short-chain fatty acids, and that Ca2+ ions might be an important mediator for these secretagogues in the acinar cells of the pancreas of sheep.
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