Influence of trifluoperazine on ACTH- or angiotensin-stimulated mineralocorticoid and glucocorticoid secretion in man.
During stimulation of adrenocortical secretion the calcium--calmodulin system is activated to a different extent, depending on the secretagogue substance. In the submitted paper the influence of therapeutic doses of the calmodulin inhibitor, trifluoperazine, on aldosterone and cortisol secretion stimulated by ACTH or by activation of endogenous angiotensin by furosemide was investigated in healthy subjects. Trifluoperazine already in amounts of 6 mg/day administered for one week inhibited the "basal" aldosterone secretion assessed in a vertical position (p less than 0.01) and ACTH stimulated secretion (during the 30th minute p less than 0.05). The basal aldosterone secretion assessed in a horizontal position was not affected by trifluoperazine, similarly as it did not affect the secretory response to endogenous angiotensin activated by furosemide, regardless whether a dose of 6 mg or 12 mg/day was used. ACTH stimulated cortisol blood levels were after trifluoperazine insignificantly but constantly lower throughout the test, while they were not altered by trifluoperazine in the furosemide test. The plasma calcium level was not significantly affected by trifluoperazine. It may be concluded that trifluoperazine alters ACTH stimulated mineralocorticoid secretion, while it does not influence angiotensin stimulated secretion. The revealed differences in adrenocortical response to trifluoperazine in vivo cannot be explained merely by a different sensitivity of the calcium-calmodulin system to stimulation by two different secretagogues, but by interaction of some regulatory mechanisms influenced by trifluoperazine with adrenocortical secretion.
Zofková
I
I
Research Institute of Endocrinology, Prague, Czechoslovakia.
Hampl
R
R
D000302:Adrenal Cortex / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D000809:Angiotensins / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014268:Trifluoperazine / Q000494:pharmacology*
D000809:Angiotensins; D014268:Trifluoperazine; D000450:Aldosterone; D005665:Furosemide; D000324:Adrenocorticotropic Hormone; D002118:Calcium; D006854:Hydrocortisone