Activation of rat kidney adenylate cyclase by vasopressin analogues: lack of correlation with antidiuretic activity.
Vasopressin analogues with enhanced antidiuretic activity in vivo (deamino-[D-arg8]-vasopressin, deamino-6-carba-[Orn8]-vasopressin, deamino-6-carba-[Arg8]-vasopressin, and deamino-6-carba-[D-Arg8]-vasopressin) were tested for their ability to activate rat renal medullary adenylate cyclase and compared to the natural antidiuretic hormones [Arg8]- and [Lys8]-vasopressin. The enzyme preparation used did not inactivate the vasopressins or the analogues tested. The analogues activated adenylate cyclase. However, several of them were far less effective than expected on the basis of their very high in vivo antidiuretic activity. It was concluded that the enhanced in vivo activity reflects greater metabolic stability in vivo rather than enhanced affinity for the renal antidiuretic hormone receptor.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D007668:Kidney / Q000201:enzymology*; D007679:Kidney Medulla / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D013329:Structure-Activity Relationship; D013552:Swine; D014667:Vasopressins / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*
D014667:Vasopressins; D000262:Adenylyl Cyclases