Impaired Ca²⁺ signaling in exocrine acinar cells in double knockout mice of type 2 and type 3 IP3 receptors

Abstract

It is generally considered that exocrine secretion is mediated by [Ca²⁺]_i increases in acinar cells. We investigated Ca²⁺ signaling in the exocrine tissues of the double knockout mice lacking inositol 1,4,5-trisphosphate receptors type2 (IP3R2) and type3 (IP3R3), in which exocrine dysfunctions were seen, in order to know Ca²⁺ signaling the contribution of these receptors to exocrine secretion. Muscarinic receptor (mAChR)-induced [Ca²⁺]_i increases were severely impaired in the salivary gland acinar cells prepared from the double mutants, while those in single knockout mice of IP3R2 or IP3R3 was only slightly reduced, compared to those in the wild-type mice. Next, agonist-induced [Ca²⁺]_i changes were similarly examined in pancreatic acinar cells. Pancreatic acinar cells dissociated from the double mutants failed to show the [Ca²⁺]_i increases in response to ACh or cholecystokinin. In contrast, acinar cells prepared from single knockout mice of IP3R2 or IP3R3 showed the Ca²⁺ signaling similar to that in the wild-type mice: the [Ca²⁺]_i increases initiated at the apical pole, propagated to the basal regions as Ca²⁺ waves and oscillated, suggesting the redundant role for IP3R2 and IP3R3. These results demonstrate that the severe impairment of exocrine secretion in the IP3R2/IP3R3 double knockout mice was due to the lack of Ca²⁺ signaling in these glands and that IP3R2 and IP3R3 are the major receptor subtypes responsible for the physiological function in exocrine cells. [Jpn J Physiol 55 Suppl:S134 (2005)]