Effects of TMB-8 and dantrolene on ACTH- and angiotensin-induced steroidogenesis by frog interrenal gland: evidence for a role of intracellular calcium in angiotensin action.
The influence of intracellular calcium on the steroidogenic response of adrenocortical tissue to ACTH and angiotensin has been studied in the frog, using a perifusion system technique. The release of corticosterone, aldosterone and prostaglandins in the effluent medium was monitored by specific radioimmunoassays. TMB-8 and dantrolene, two potential blockers of calcium mobilization from intracellular pool(s), were tested. Dantrolene (5 X 10(-5) M) significantly reduced basal and angiotensin-induced corticosterone and aldosterone production but had little effect on ACTH-evoked steroid release. Conversely TMB-8 (10(-4) M) profoundly depressed spontaneous as well as ACTH- and angiotensin II-induced corticosteroid secretion, suggesting that this compound may affect not only calcium mobilization from the endoplasmic reticulum pool but also calcium influx. Adrenal glands perifused with both dantrolene and calcium-free medium showed no response to angiotensin II. Conversely, in calcium-free conditions and in the presence of dantrolene, angiotensin II still caused an increase in prostaglandin synthesis. Taken together, these results indicate that 1) dantrolene is a more specific agent than TMB-8 in inhibiting calcium mobilization from intracellular pool(s); 2) ACTH increases corticosteroidogenesis without inducing mobilization of intracellular calcium; 3) angiotensin II stimulates both the efflux of calcium from the endoplasmic reticulum and the influx of calcium through the plasma membrane; 4) calcium is required after prostaglandin production in the steroidogenic response of frog interrenal gland to angiotensin II.
Lihrmann
I
I
UA CNRS 650, Unité Alliée à l'INSERM, Faculté des Sciences, Université de Rouen, Mont-Saint-Aignan, France.
Delarue
C
C
Homo-Delarche
F
F
Feuilloley
M
M
Bélanger
A
A
Vaudry
H
H
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis; D003620:Dantrolene / Q000494:pharmacology*; D015232:Dinoprostone; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism; D011895:Rana ridibunda
D000305:Adrenal Cortex Hormones; D002121:Calcium Channel Blockers; D011458:Prostaglandins E; D000804:Angiotensin II; D000450:Aldosterone; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D000324:Adrenocorticotropic Hormone; D003620:Dantrolene; D015232:Dinoprostone; D002118:Calcium; D003345:Corticosterone