Effects of prostaglandin H 2, prostaglandin E 2, and arachidonic acid on parathyroid hormone and antidiuretic hormone activation of rat kidney adenylate cyclase

Abstract

These experiments examine interactions of arachidonic acid; the substrate for prostaglandin cyclooxygenase, prostaglandin (PG)H 2, a key endoperoxide intermediate in prostaglandin synthesis; and prostaglandin (PG)E 2, an important prostaglandin produced within the kidney; with adenylate cyclase activity in renal cortex, outer medulla, and inner medulla. In addition, the effects of arachidonic acid, PGH 2, and PGE 2 on parathyroid hormone (PTH) activation of adenylate cyclase in cortex, and of antidiuretic hormone (ADH) activation of that enzyme in outer and inner medulla are examined. Arachidonic acid elicited a concentration-dependent inhibition of basal and PTH-stimulated adenylate cyclase activity in renal cortex. Concentration-dependent inhibition by arachidonic acid of basal and ADH-stimulated adenylate cyclase activity was observed in outer and inner medulla. PGH 2 inhibited basal activity in all three areas of the kidney. There was also inhibition by PGH 2 of medullary ADH and cortical PTH stimulation. PGE 2 stimulated adenylate cyclase in all three areas. PGE 2 had no effect upon PTH stimulation in cortex and was additive with ADH in outer and inner medulla. PGE 2 stimulation was inhibited by arachidonic acid, and this inhibition seemed competitive. Inhibition by both arachidonic acid and PGH 2 was not destructive. Experiments with [1- 14C]arachidonic acid and indomethacin suggest that the inhibition by arachidonic acid was actually mediated by arachidonic acid and not a metabolite. Both PGH 2 and arachidonic acid inhibition was independent of phosphodiesterase. This activation by product, PGE 2, and inhibition by its precursors, arachidonic acid and PGH 2, provide a possible mechanism by which the prostaglandin system could modulate adenylate cyclase responsiveness to hormonal activation.