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Downregulation of vasopressin V 1A receptors and activation of mitogen‐activated protein kinase in rat mesangial cells cultured under high‐glucose conditions
Author(s) -
Tahara Atsuo,
Tsukada Junko,
Tomura Yuichi,
Yatsu Takeyuki,
Shibasaki Masayuki
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05693.x
Subject(s) - staurosporine , mesangial cell , protein kinase c , endocrinology , medicine , downregulation and upregulation , mapk/erk pathway , protein kinase a , receptor , signal transduction , vasopressin , extracellular , biology , mitogen activated protein kinase , kinase , chemistry , microbiology and biotechnology , biochemistry , kidney , gene
Summary In the present study we examined the effects of high extracellular glucose concentrations on vasopressin ( AVP ) V 1A receptor kinetics and signal transduction in cultured rat mesangial cells. Scatchard analysis of [ 3 H ]‐ AVP binding to mesangial cell plasma membranes showed that although high glucose (30 mmol/L) decreased V 1A receptor numbers relative to cells cultured in normal glucose (10 mmol/L), receptor affinity was not affected. This V 1A receptor downregulation was associated with an attenuated increase in AVP ‐stimulated cytosolic free calcium concentrations ([ C a 2+ ] i ). In addition, high glucose increased both the basal and AVP ‐stimulated activity of the classic mitogen‐activated protein kinase, namely extracellular signal‐regulated kinase ( ERK ). Furthermore, high glucose induced activation of protein kinase C ( PKC ) in mesangial cells that could be inhibited by coincubation with the PKC inhibitor staurosporine (10 nmol/L). Staurosporine also markedly attenuated the high glucose‐induced downregulation of V 1A receptors on mesangial cells and blocked the depressed [ C a 2+ ] i response and increased ERK activity induced by AVP . The results indicate that high extracellular glucose downregulates V 1A receptors on rat mesangial cells and modulates their signal transduction properties via PKC activation.