Dual effects of fluoroaluminate on activation of calcium influx and inhibition of agonist-induced calcium mobilization in rat glomerulosa cells.
Results presented in this study demonstrate that, in rat glomerulosa cells, fluoroaluminate (AlF4-) alone stimulates both cAMP accumulation (maximal stimulation 10-fold, ED50, 24 mM) and total inositol phosphate accumulation (maximal stimulation 12-fold, ED50 14 mM). Despite a transient accumulation of Ins(1,4,5)P3 after AlF4- stimulation, no rapid and transient intracellular calcium mobilization was observed. In contrast to angiotensin II (Ang II) or vasopressin (AVP), AlF4- induces only a slow and sustained increase in intracellular Ca2+. We demonstrate that this increase results from a Ca2+ influx mediated by cAMP-protein kinase A (PKA) pathway since preincubation with H-89, a potent PKA inhibitor, inhibits this influx. Moreover, a short preincubation (15 min at 37 degrees C) of cells with AlF4- or ACTH prevents the initial release of Ca2+ from intracellular stores induced by Ang II, but does not affect the amount of InsPs accumulated under Ang II stimulation. This rapid inhibition of Ang II action is mediated by ACTH- or AlF4(-)-stimulated cAMP production since pretreatment with H-89 leads to a complete reversal. cAMP most likely acts at the level of Ins(1,4,5)P3 receptors since an increase in intracellular cAMP blunts the calcium response induced by addition of exogenous Ins(1,4,5)P3 to permeabilized cells. These results point out that, in rat glomerulosa cells, activation of the cAMP pathway can induce a rapid desensitization of the phospholipase C pathway by acting downstream of inositol phosphate accumulation.
Grazzini
E
E
INSERM U 401, CCIPE, Montpellier, France.
Guillon
G
G
Chouinard
L
L
Gagnon
J S
JS
Prezeau
L
L
Gallo-Payet
N
N
D000262:Adenylyl Cyclases / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005461:Fluorine / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000502:physiology; D014667:Vasopressins / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D010716:Phosphatidylinositols; D014667:Vasopressins; D000804:Angiotensin II; C053629:fluoroaluminum; D005461:Fluorine; D000324:Adrenocorticotropic Hormone; D000535:Aluminum; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D002118:Calcium