Possible role of calcium uptake and calmodulin in adrenal glomerulosa cells: effects of verapamil and trifluoperazine.

The effects of verapamil and trifluoperazine were examined on isolated rat adrenal glomerulosa cells so as to assess the role of calcium ion influx and calmodulin in the function of this cell population. Verapamil (10(-5) and 10(-4) moles/1) slightly reduced the basal production rate of aldosterone and strongly inhibited the response to angiotensin II, potassium ions, corticotrophin (ACTH) and dibutyryl cyclic AMP (db-cAMP). The concentration of verapamil required to reduce the response to these agonists by 50% varied between 2 and 6 mumoles/1. Trifluoperazine (30 mumoles/1) slightly increased the basal production rate of aldosterone. The response to angiotensin and potassium was variably antagonized by 3 mumoles/1 trifluoperazine and completely inhibited by the drug at 30 mumoles/1. The antagonist at a concentration of 3 mumoles/1 exerted either a facilitatory or inhibitory effect on the response to ACTH and db-cAMP, depending on the concentration of the agonist. Trifluoperazine at a concentration of 30 mumoles/1 reduced the response to both agonists to a level which was 2-3 fold higher than that observed in appropriate control samples. The present results indicate that (1) calcium influx is an essential event in the aldosterone stimulating action of angiotensin II, potassium ions, ACTH and cyclic AMP; (2) stimulation by angiotensin II and potassium ions are completely dependent on calmodulin; (3) stimulation by ACTH and cyclic AMP is mediated by calmodulin-dependent and independent mechanisms.