Cell-specific expression of the IP3 receptor gene family in the kidney

Background/Aim: The localization of inositol trisphosphate (IP3) receptor isoforms, types 1-3, in the kidney and their role in the regulation of the intracellular calcium concentration - [Ca2+](i) - are discussed. Methods: Immunohistological studies with isoform-specific antibodies were performed to reveal the localization of IP3 receptor isoforms, To examine the role of IP3 receptor type 1 in the glomeruli, the responses of [Ca2+](i) to hormonal stimuli were examined in IP3 receptor type 1 knockout mice. Results: In the immunohistological study, type 1 receptor was present in arteries, afferent arterioles, and mesangial cells. Double staining with antibodies against aquaporin 2 and IP3 type 2 receptor revealed that type 2 receptor was localized mainly in the intercalated cells. The type 3 receptor showed characteristic intracellular localization in the collecting duct cells of the cortex to the outer medulla. Immunostaining of type 3 receptor was most intense in the cytoplasm on the basolateral membrane side and was not seen on the apical side. The responses of [Ca2+](i) to angiotensin II and endothelin in the glomeruli were markedly attenuated in IP3 receptor type 1 knockout mice. Conclusions: The three isoforms of the IP3 receptor showed distinctive localization in the kidney, and the type 1 receptor plays a major role in the regulation of [Ca2+](i) in the glomeruli. The physiological significance of the cell-specific localization, however, remains to be determined. Copyright (C) 2000 S. Karger AG, Basel.