VASOPRESSIN-PROSTAGLANDIN INTERACTIONS IN ISOLATED TUBULES FROM RAT OUTER MEDULLA

Abstract

Interactions between AVP [8-Arg-vasopressin] and prostaglandins [PG] were investigated in MaL [medullary thick ascending limb of Henle''s loop] and MCT [medullary collecting tubule] microdissected from the rat outer medulla. Incubation of MCT with 14C-arachidonic acid resulted in the formation of 14C-PGE2 and 14C-PGF2.alpha.; when MAL was incubated under the same condition, only traces of PG were formed. PG synthesis in MCT was inhibited (-50%) by the PG cyclooxygenase inhibitor ibuprofen (10-6 M). Preincubation with ibuprofen enhanced the stimulation of adenylate cyclase by 5 .times. 10-9 M AVP in MCT but decreased the stimulation of adenylate cyclase by AVP in MAL. The effects of a 2nd PG cyclooxygenase inhibitor, naproxen (10-5 M), were similar to those of ibuprofen. Ibuprofen did not influence cyclic AMP phosphodiesterase activity in MCT or in MAL. Exogenous PGE2 or PGF2.alpha. (10-6 M) had no effect on either basal or AVP-stimulated adenylate cyclase activity in MCT. Apparently MCT but not MAL is a site of active synthesis and accumulation of PG. Although both MAL and MCT have AVP-sensitive adenylate cyclase, incubation with PG cyclooxygenase inhibitors have, in the presence of arachidonic acid, an opposite effect on this enzyme in these 2 segments, resulting in increased AVP stimulation in MCT and decreased stimulation in MAL. Products of PG synthesis from arachidonic acid inhibit AVP-sensitive adenylate cyclase activity in MCT but not that located in MAL. The primary PG (PGE2, PGF2.alpha.) are probably not responsible for AVP modulation in MCT.