ADH-sensitive cAMP system in papillary collecting duct: effect of osmolality and PGE2

Abstract
The papillary collecting duct (PCD) is considered to be of major importance in the final elaboration of the urine, but the metabolism of cAMP has not been directly studied in the PCD. The present study examined the basic properties of the cAMP system in isolated PCD microdissected from rat kidney. Vasopressin (VP) caused a marked (5- to 10-fold) stimulation of adenylate cyclase (AC) but parathyroid hormone, calcitonin, isoproterenol and bradykinin were without effect. A gradual increase in osmolality from 200 mosM had a biphasic effect on AC, first enhancing (at 800 mosM) then inhibiting AC activity at 2,000 mosM. cAMP-phosphodiesterase activity was inhibited as osmolality was increased from 200 to 800 mosM and the inhibition remained constant to 2,000 mosM. Incubation of intact PCD with VP resulted in a 3-fold increase in cAMP levels. As the osmolality of the incubation medium was increased from 300 to 2,000 mosM, both basal and VP-stimulated cAMP levels continued to increase. Prostaglandin E2 (PGE2) (10-5 M) alone (in the absence of VP) caused an increase in AC activity, but the same dose of PGE2 had no effect on AC activity stimulated by submaximal or maximal doses of VP. PGE2 (10-5 M) caused a small increase in cAMP levels in intact PCD. PGE2 inhibited VP-stimulated cAMP levels by 50%. Incubation of PCD with PGE2 had no effect on cAMP-phosphodiesterase activity. Osmolality in the physiologic range has a major influence on cAMP metabolism in the PCD and there is an apparent antagonism between PGE2 and VP at the level of cAMP accumulation in the PCD.

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