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.