Bradykinin and angiotensin II activation of arachidonic acid deacylation and prostaglandin E2 formation in rabbit kidney. Hormone-sensitive versus hormone-insensitive lipid pools of arachidonic acid.

The isolated perfused rabbit kidney was used to characterize the hormone-sensitive lipid pool from which esterified arachidonic acid is hydrolyzed by the vasoactive hormone bradykinin. The kidney lipids were labeled with radioactive arachidonic acid and the specific activities (counts per min/ng) of the prostaglandin Ez released with or without hormone stimulation were compared. The results indicated the following. 1) The specific activity of prostaglandin Ez released under basal (no hormone stimulation) conditions was 4 to 5fold higher than the corresponding value after bradykinin administration. The prostaglandin Ez fractions obtained in the absence or presence of bradykinin thus originate from two functionally different pools of esterified arachidonate, designated the hormone-insensitive and the hormone-sensitive pools, respectively. 2) Infusion of exogenous arachidonate to a kidney which was prelabeled with radioactive acid caused the release of prostaglandin Ea having a specific activity markedly higher than that of basal prostaglandin Ez, indicating that exogenous arachidonate is incorporated mainly into the hormone-insensitive pool. 3) During the course of the kidney perfusion experiment, the specific activity of the bradykinin-stimulated prostaglandin EP is gradually increasing. This trend is accelerated if the kidney is repeatedly stimulated with the hormone. We conclude that the rate of arachidonate incorporation into the hormone-sensitive pool is relatively slow and is controlled by the extent to which the pool has been depleted by prior hormone stimulation. Repeated stimulations cause radioactive arachidonate from the hormone-insensitive pool to be transferred to the hormone-sensitive pool to replace the arachidonate that had been hydrolyzed and converted to prostaglandins. Characterization of the hormone-sensitive pool by specific labeling with radioactive arachidonic acid would thus be best achieved under conditions which induce prior release of nonradioactive acid from this pool.