Differential regulation of agonist-stimulated Ca2+ influx in acini of rat pancreas and submandibular gland.
In order to characterize agonist-dependent Ca2+ influx pathways, changes in cystolic Ca2+ (Ca2+i) during stimulation with multiple Ca(2+)-mobilizing agents were measured in rat pancreatic and submandibular gland acini loaded with fura-2. In pancreatic acini, maximal levels of carbachol and cholecystokinin octapeptide (CCK-8) produced virtually identical changes in Ca2+i when added alone or together: an immediate increase to 4-5 times resting Ca2+i followed by a decline to a steady-state level 2-3 times resting, which was unchanged by another stimulus. In submandibular gland acini, maximal carbachol stimulation increased Ca2+i 3-4-fold followed by a plateau at 2-3 times resting, which was further increased by epinephrine. Epinephrine alone increased steady-state Ca2+i to 53 +/- 18% (n = 21) of that observed with carbachol. Stimulation with both agents increased the steady-state plateau level of Ca2+i to 144 +/- 28% of that during exposure to carbachol alone (n = 11, p < 0.05). When changes in Ca2+i due solely to Ca2+ influx were measured, carbachol and epinephrine together increased Ca2+i during the steady-state phase to 149 +/- 31% of that measured with carbachol alone (n = 8, p < 0.05). Atropine blocked only responses to carbachol, prazosin blocked only responses to epinephrine and L 364,718 blocked only CCK-8-induced changes in Ca2+i. Thus, in pancreatic acini, a single agonist-sensitive Ca2+ influx pathway is linked independently to muscarinic cholinergic and peptidergic (CCK-8) receptors. In contrast, submandibular gland acini contain functionally separate agonist-sensitive Ca2+ influx pathways, which are independently linked to muscarinic and to alpha-1 adrenergic receptors.
Hurley
T W
TW
Department of Child Health, University of Missouri School of Medicine, Columbia 65212.
Brinck
R W
RW
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D016257:Fura-2; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology; D013363:Submandibular Gland / Q000378:metabolism*
D011949:Receptors, Cholecystokinin; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D012844:Sincalide; D002118:Calcium; D016257:Fura-2; D011224:Prazosin; D004837:Epinephrine