Role of calcium in stimulus-secretion coupling on isolated frog interrenal gland.
The influence of extracellular calcium concentration on the steroidogenic response to ACTH and to the angiotensin II analogue [Sar1-Val5]AII has been studied in the frog, using a perfusion system technique. The release of corticosterone and aldosterone in the effluent medium was measured by specific radioimmunoassays. In calcium-free medium the stimulatory effect of ACTH (10(-9) M) was completely abolished whereas the response to dbcAMP (5 mM) was unchanged indicating that the role of calcium takes place before the formation of cAMP. Conversely, in the absence of calcium, angiotensin II (10(-7) M) was still able to stimulate corticosterone and aldosterone production. Addition of Co2+ (4 mM), a calcium antagonist, to the perfusion medium, inhibited partially the response of adrenal tissue to ACTH, dbcAMP and angiotensin. The voltage-dependent calcium channel blocker verapamil (10(-6) induced a dose-related inhibition of the corticotropic effect of ACTH. At the higher dose (10(-4) M), verapamil totally inhibited the stimulation of corticosterone and aldosterone production induced by ACTH. By contrast, at the same dose it did not alter the stimulatory effect of forskolin (2.4 X 10(-7)M) on corticosterone output, but significantly diminished forskolin-induced aldosterone response. Similarly, angiotensin-stimulated corticosterone production was slightly inhibited by 10(-4) M verapamil, whereas aldosterone response to angiotensin was totally abolished, indicating that verapamil may act intracellularly to block the conversion of corticosterone to aldosterone. Taken together, these results indicate that, in amphibians extracellular calcium is essential for the action of ACTH, either for the binding of the hormone to its receptor and/or for the transduction of the information from hormone-receptor complex to the adenylate cyclase moiety and that the mechanism of action of angiotensin does not involve calcium uptake by adrenocortical cells.
I
I
Lihrmann
C
C
Delarue
M
M
Feuilloley
E
E
Escher
P
P
Netchitailo
F
F
Leboulenger
H
H
Vaudry
D000311:Adrenal Glands / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003035:Cobalt / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis; D066298:In Vitro Techniques; D007401:Interrenal Gland / Q000187:drug effects* / Q000378:metabolism; D007473:Ion Channels / Q000502:physiology; D008297:Male; D011895:Rana ridibunda; D014700:Verapamil / Q000494:pharmacology
D007473:Ion Channels; D000804:Angiotensin II; D005576:Colforsin; D003035:Cobalt; D000450:Aldosterone; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D014700:Verapamil; D002118:Calcium; D003345:Corticosterone