Pancreatic acinar cells: acetylcholine-induced membrane depolarization, calcium efflux and amylase release.
1. The effects of acetylcholine upon the output of amylase, Ca(2+) efflux and membrane potential of pancreatic acinar cells have been measured in segments of mouse pancreas superfused in vitro.2. Amylase output was measured continuously using an on-line automated fluorimetric method; Ca(2+) efflux was monitored by measuring the release of (45)Ca(2+) from pre-labelled tissue; and intracellular recordings of acinar transmembrane potentials were obtained with glass micro-electrodes. In some experiments membrane potentials, and in others (45)Ca(2+) efflux, were measured concomitantly with amylase release.3. Acetylcholine depolarized the acinar cells, increased tissue (45)Ca(2+) efflux and raised amylase output, each with a similar dose-dependence, i.e. a maximal response at 10(-5)M, threshold =/< 10(-8)M, and ED(50) values of 0.7 x 10(-7)M, 0.5 x 10(-7)M, and 2 x 10(-7)M for depolarization, amylase release, and (45)Ca(2+) efflux, respectively.4. In response to acetylcholine both depolarization and (45)Ca(2+) efflux preceded or coincided with the increase in amylase output.5. Acetylcholine 10(-5)M and [K](0) 47 mM were without effect on (45)Ca(2+) efflux in the presence of atropine (3 x 10(-6)M) but pancreozymin (0.3 u./ml.) still elicited a marked increase in (45)Ca(2+) release.6. These results suggest that the stimulatory action of acetylcholine on the pancreatic acinar cell involves, sequentially, a specific receptor-activated increase in membrane permeability, depolarization, Ca(2+) mobilization and amylase release. These events are discussed in relation to the integrated mechanism of stimulus-secretion coupling.
D000109:Acetylcholine / Q000494:pharmacology*; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002127:Calcium Isotopes; D002463:Cell Membrane Permeability / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005470:Fluorometry; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000187:drug effects; D013268:Stimulation, Chemical; D013997:Time Factors
D002127:Calcium Isotopes; D001285:Atropine; D002766:Cholecystokinin; D000681:Amylases; D000109:Acetylcholine; D002118:Calcium