Effects of Ca++ and prostaglandin E1 on vasopressin activation of renal adenyl cyclase.
Adenyl cyclase activity was assayed in crude homogenates of the renal cortex, medulla, and papilla of the golden hamster. The specific activity (moles C-AMP/unit of time per mg protein of tissue) of the enzyme under basal conditions, was greatest in papilla, somewhat lower in medulla, and least in cortex. On an absolute scale, the sensitivity to vasopressin was greater in the medullary and papillary than in the cortical homogenates. In addition, at concentrations of 0.1-1.0 mm, CaCl(2) inhibited the enzyme in the order papilla > medulla > cortex. These results imply the existence of distinct differences in the composition of the adenyl cyclase-receptor complex in various parts of the kidney. We proposed that Ca(++) inhibits the core enzyme directly since at the minimally inhibitory concentration (0.1 mm), CaCl(2) reduced to an equivalent extent (a) basal activity, (b) the response to graded doses of vasopressin (0.5 to 50.0 mU/ml) and (c) the response to maximal stimulatory concentrations of NaF (10 mm). Prostaglandin E(1) (PGE(1) = 10(-7)m) had no effect on either basal adenyl-cyclase activity or the response to 10 mm NaF in medullary and papillary homogenates. 7-Oxa-13-prostynoic acid (10(-4)m) similarly had no effect under basal conditions or on stimulation with NaF in medullary homogenates. Both fatty acids, however, inhibited the enzymic response to vasopressin, particularly at low concentrations of the peptide. The straight-chain fatty acid, 11-eicosanoic acid (10(-7)m), was inactive on basal activity or on the response to vasopressin. The possibility that PGE(1) modifies the coupling mechanism between the core enzyme and the hormone-specific receptor is discussed.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism*; D003864:Depression, Chemical; D005227:Fatty Acids / Q000494:pharmacology; D005260:Female; D005459:Fluorides / Q000494:pharmacology; D007477:Ions; D007668:Kidney / Q000201:enzymology*; D011453:Prostaglandins / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D002712:Chlorides; D005227:Fatty Acids; D007477:Ions; D011453:Prostaglandins; D014667:Vasopressins; D012964:Sodium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D005459:Fluorides; D002118:Calcium