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Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney

1998; Elsevier BV; Volume: 54; Linguagem: Inglês

10.1046/j.1523-1755.1998.06705.x

1523-1755

Jia L. Zhuo, Rachael Dean, Christine Maric, P. Aldred, P. Harris, Daine Alcorn, Frederick A.O. Mendelsohn,

Ion Transport and Channel Regulation

Localization and interactions of vasoactive peptide receptors in renomedullary interstitial cells of the kidney. Vasoactive peptides regulate renal medullary microcirculation and tubular function, but the localization of their receptors and mechanisms of actions are currently unknown. Using electron microscopic autoradiography, we have mapped the receptors for angiotensin II (Ang II [AT 1 and AT 2 ]), endothelin (ET A and ET B ), and bradykinin (B 2 ) in the rat renal medulla. Although these peptide receptors show distinct vascular and tubular distributions, they overlap strikingly in renomedullary interstitial cells (RMICs) of the inner stripe and the papilla. Using reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis, mRNAs for AT 1A , ET A , and B 2 receptors were detected in cultured adult RMICs. Ang II increases intracellular inositol 1,4,5-triphosphate (IP 3 ) and [Ca 2+ ] i and stimulates [ 3 H]thymidine incorporation and extracellular matrix (ECM) synthesis via AT 1A receptors. Endothelin and bradykinin also stimulate cell proliferation and ECM synthesis in RMICs through ET A and B 2 receptors, respectively, but the actions of endothelin are modulated by concurrent nitric oxide production. By contrast, AT 2 receptor mRNA was detected only in embryonic RMICs, in which Ang II inhibits cell proliferation through this receptor. These results suggest that multiple vasoactive peptides may interact with RMICs to exert endocrine and/or paracrine influences on renal medullary microcirculation and tubular function.