Cholinergic stimulation of ion fluxes in pancreatic islets.
Cholinergic agents are known to stimulate the hydrolysis of polyphosphoinositides in pancreatic islets. The effect of carbamylcholine upon ion fluxes in the islet cells was investigated. Carbamylcholine provoked a rapid but poorly sustained increase in 45Ca and 86Rb outflow from perifused islets. Such a cationic response was observed at different glucose concentrations (zero to 16.7 mM), at three concentrations of carbamylcholine (10 microM, 100 microM and 1.0 mM), and in the absence or presence of extracellular Ca2+. It coincided with a biphasic stimulation of insulin release, both the cationic and secretory responses being abolished in the presence of atropine (10 microM). At variance with nutrient secretagogues, carbamylcholine failed to affect the net production of cyclic AMP and caused a transient decrease in 32P outflow from islets prelabelled with [32P]phosphate. It is proposed that cholinergic agents mobilize Ca2+ from intracellular sites, possibly through generation of inositol, 1,4,5-triphosphate from phosphatidylinositol 4,5-bisphosphate. The intracellular redistribution of Ca2+ does not appear sufficient, however, to account fully for the secretory response, which may also involve activation of protein kinase C by diacylglycerol.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002132:Calcium Radioisotopes / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D011868:Radioisotopes; D051381:Rats; D012413:Rubidium / Q000378:metabolism*
D002132:Calcium Radioisotopes; D007328:Insulin; D011868:Radioisotopes; D004533:Egtazic Acid; D001285:Atropine; D002217:Carbachol; D005947:Glucose; D012413:Rubidium