Jpn. J. Pharmacol. 84 (1), 25-31 (2000)

Characterization of the Ca²⁺ Response Mediated by Activation of b-Adrenoceptors in Rat Submandibular Ducts

Akihiro Nezu, Akihiko Tanimura and Yosuke Tojyo

Department of Dental Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan

Abstract: The Ca²⁺ signaling mediated by activation of b-adrenoceptors was studied in a purified preparation of ducts from rat submandibular glands. At concentrations above 1ﾊ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 b-adrenoceptor antagonist propranolol but not by the a-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 b-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.

Keywords: Submandibular duct, b-Adrenoceptor, Cytosolic Ca²⁺, Isoproterenol, Cyclic AMP