Inhibition of low threshold calcium channels by angiotensin II in adrenal glomerulosa cells through activation of protein kinase C.
In adrenal glomerulosa cells, low threshold voltage-activated (T-type) calcium channels play a crucial role in coupling physiological variations of extracellular potassium to aldosterone biosynthesis. Angiotensin II markedly reduced the activity of these channels by shifting their activation curve toward positive voltage values. This inhibition of the channels resulted in a marked decrease of the cytosolic free calcium concentration maintained by potassium. This effect was abolished by losartan, a specific antagonist of the angiotensin II AT1 receptor. Hormone action on T-type channels appeared to be mediated by protein kinase C because 1) it was mimicked by phorbol ester and diacylglycerol, and 2) it was significantly reduced by decreasing protein kinase C activity with specific inhibitors such as chelerythrine chloride or a pseudosubstrate of the enzyme, as well as by protein kinase C down-regulation. Similarly, protein kinase C activation reduced the cytosolic calcium response to potassium and the steroidogenic action of this agonist. Low threshold T-type calcium channels therefore appear as potential sites for the modulation of steroidogenesis by protein kinase C in adrenal glomerulosa cells.
Rossier
M F
MF
Division of Endocrinology, University Hospital, Geneva, Switzerland.
Aptel
H B
HB
Python
C P
CP
Burnay
M M
MM
Vallotton
M B
MB
Capponi
A M
AM
D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D002417:Cattle; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D004347:Drug Interactions; D004789:Enzyme Activation; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000187:drug effects / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004075:Diglycerides; C044295:1,2-dioctanoylglycerol; D000804:Angiotensin II; D000450:Aldosterone; C038237:1-oleoyl-2-acetylglycerol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium