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SYMPOSIUM Experimental Biology 1995 Endothelin Receptors: Role in Renal Function and Dysfunction SIGNALLING PATHWAYS ACTIVATED BY ENDOTHELIN STIMULATION OF RENAL CELLS
Author(s) -
Nord Edward P
Publication year - 1996
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.1440-1681.1996.tb02833.x
Subject(s) - endothelin receptor , stimulation , receptor , signalling pathways , endothelin 1 , function (biology) , microbiology and biotechnology , biology , neuroscience , endocrinology , medicine
SUMMARY 1. Endothelin mediates its effects in a variety of renal cells via a multiplicity of intracellular signalling pathways. 2. Stimulation of phosphatidylinositol‐specific phospholipase C (PI‐PLC), resulting in the activation of inositol trisphosphate and diacylglycerol, can be detected even at picomolar concentrations of peptide. 3. Endothelin activation of cPLA 2 is sensitive to ambient [Ca 2+ ] i , is not contingent upon protein kinase C activation and is independent of PI‐PLC stimulation, being coupled to the endothelin receptor in a yet to be determined manner. 4. Activation by endothelin of phosphatidylcholine‐specific phospholipase D is under the dual regulation of protein kinase C and [Ca 2+ ] i , with protein kinase C being the major regulator and [Ca 2+ ] i playing a secondary, modulatory role. 5. Phosphatidylcholine‐specific phospholipase C (PC‐PLC) is stimulated by endothelin and accounts for the prolonged activation of diacylglycerol by this peptide. PC‐PLC activity is critically dependent upon [Ca 2+ ] i , whereas protein kinase C plays no role in modulating the activity of this enzyme. 6. Endothelin enhances the phosphorylation of protein tyrosine kinases, with evidence that phosphorylation of pp 60 Src may be an important early event.