Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin.
By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D015232:Dinoprostone; D004789:Enzyme Activation; D004848:Epithelium / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D005480:Flurbiprofen / Q000494:pharmacology; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007684:Kidney Tubules / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D011458:Prostaglandins E / Q000096:biosynthesis*; D011817:Rabbits; D017981:Receptors, Neurotransmitter / Q000032:analysis / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007473:Ion Channels; D009479:Neuropeptides; D010716:Phosphatidylinositols; D011458:Prostaglandins E; D017981:Receptors, Neurotransmitter; D010566:Virulence Factors, Bordetella; D000804:Angiotensin II; D001127:Arginine Vasopressin; D005480:Flurbiprofen; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D001920:Bradykinin; D002118:Calcium