The stimulatory effect of endothelin-1 on frog adrenocortical cells is mediated through both the phospholipase C and the adenylyl cyclase transduction pathways.
We have previously shown that endothelin-1 (ET-1) stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ET(A) receptors. In the present study, we have investigated the transduction pathways involved in the corticotropic action of ET-1. Exposure of frog adrenal explants to ET-1 provoked a time- and dose-dependent increase in inositol phosphate production and a parallel decrease in membrane polyphosphoinositide content. Incubation of adrenal explants with ET-1 also induced a dose-related increase of cAMP formation. The selective ET(A) receptor antagonist BQ-485 totally abolished the stimulatory effects of ET-1 on both inositol phosphate and cAMP production. In contrast, the selective ET(B) receptor agonist IRL 1620 did not significantly modify polyphosphoinositide hydrolysis or cAMP formation. Administration of the phospholipase C inhibitor U-73122 or the protein kinase A inhibitor H-89 to perifused frog adrenal slices significantly reduced the stimulatory effect of ET-1 on corticosterone and aldosterone secretion. Concomitant administration of the two inhibitors almost completely suppressed the corticotropic effect of ET-1. Taken together, these data indicate that, in the frog adrenal gland, the stimulatory effect of ET-1 on corticosteroid secretion is mediated through activation of both the phospholipase C and the adenylyl cyclase transduction pathways.
Cartier
F
F
European Institute for Peptide Research (IFRMP 23), INSERM U-413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
Delarue
C
C
Remy-Jouet
I
I
Kodjo
M K
MK
Fournier
A
A
Vaudry
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D011895:Rana ridibunda; D017466:Receptors, Endothelin / Q000819:agonists / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides; D013997:Time Factors; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004963:Estrenes; D007295:Inositol Phosphates; D007546:Isoquinolines; D010716:Phosphatidylinositols; D011760:Pyrrolidinones; D017466:Receptors, Endothelin; D013449:Sulfonamides; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D000450:Aldosterone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D003345:Corticosterone