Characterization of the Ca2+ response mediated by activation of β-adrenoceptors in rat submandibular ducts

The Ca2+ signaling mediated by activation of beta-adrenoceptors was studied in a purified preparation of ducts from rat submandibular glands. At concentrations above 1 nM, isoproterenol (ISO) caused a small but significant increase in cytosolic Ca2+ concentration ([Ca2+](i)). The ISO-induced increase in [Ca2+](i) was completely inhibited by the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Forskolin was able to mimic the Ca2+ response to ISO. These results suggest that the ISO-induced increase in [Ca2+](i) in rat submandibular ducts is mediated by an accumulation of cAMP resulting from activation of beta-adrenoceptors. In the absence of extracellular Ca2+, ISO or forskolin caused a transient increase in [Ca2+](i), indicating Ca2+ mobilization from intracellular Ca2+ stores. Further, stimulation with ISO failed to mobilize Ca2+ after the depletion of intracellular Ca2+ stores by phenylephrine or carbachol, suggesting that the cAMP-mediated increase in [Ca2+](i) is due to a Ca2+ release from inositol trisphosphate (IP3)-sensitive Ca2+ stores. As ISO did not stimulate a detectable production of IP3, the cAMP-mediated Ca2+ mobilization may be evoked by a mechanism different from activation of phosphoinositide hydrolysis.