Interaction of forskolin with vasopressin-sensitive cyclic AMP system in renal medullary tubules.
The medullary collecting tubules (MCT) and the medullary thick ascending limb of Henle's loop (MAL) are two major sites of [8-Arg]-vasopressin (AVP) action, via cyclic AMP, on the mammalian nephron. In the present study, the effect of forskolin and forskolin in combination with AVP on accumulation of cyclic AMP in tubular segments of MAL and MCT microdissected from rat kidney was examined in vitro. Under all tested conditions, forskolin stimulated the accumulation of cyclic AMP to a greater degree in MCT than in MAL. In MAL, the effects of forskolin and AVP were synergistic; the increase in cyclic AMP after incubation with forskolin and AVP added together was 150% greater than the arithmetic sum of the increases elicited either by AVP or by forskolin alone. On the other hand, in MCT the stimulatory effects of AVP and forskolin were strictly additive. These results suggest that an intramembranous arrangement of AVP-sensitive adenylate cyclase complex differs in two types of epithelial cells located in the same tissue. The potentiating effect of forskolin on AVP-stimulated cAMP generation in MAL can be helpful in experimental studies of AVP-sensitive cyclic AMP metabolism in this nephron segment, which has a variable sensitivity to AVP in the kidneys of diverse mammalian species.
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D004224:Diterpenes; D001127:Arginine Vasopressin; D005576:Colforsin; D000242:Cyclic AMP