Cation sensitivity of inositol 1,4,5-trisphosphate production and metabolism in agonist-stimulated adrenal glomerulosa cells.
Angiotensin II (AII) evokes a biphasic increase in inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels in adrenal glomerulosa cells, with an extracellular Ca(2+)-independent early peak followed by a secondary sustained elevation that is highly dependent on the presence of extracellular Ca2+. The Ca(2+)-dependent sustained phase of agonist-induced Ins(1,4,5)P3 production was closely correlated with Ca2+ influx and was inhibited by inorganic Ca2+ channel blockers with the potency ratio: La3+ >> Cd2+ > Mn2+ > Co2+ > Ni2+. Of the two Ca2+ surrogates, Sr2+ and Ba2+, Sr2+ was partially active compared with Ca2+, and Ba2+ was inactive in restoring Ins(1,4,5)P3 formation in cells stimulated with AII in Ca(2+)-free medium. However, unlike Ca2+, Sr2+ only weakly supported and Ba2+ failed to affect the calmodulin-activation of Ins(1,4,5)P3 3-kinase. Also, there was an accumulation of Ins(1,4,5)P3 and diminished formation of Ins(1,3,4,5)P4 and Ins(1,3,4)P3 when intact glomerulosa cells were stimulated by AII in the presence of Sr2+. This difference between the Sr2+ sensitivity of phospholipase C and Ins(1,4,5)P3 3-kinase provides a means for the potentiation of agonist-induced elevations of Ins(1,4,5)P3 in the intact cell and for direct analysis of the role of the inositol tris-/tetrakisphosphate pathway in cellular signaling.
Balla
T
T
Endocrinology and Reproduction Research Branch, National Institutes of Health, Bethesda, Maryland 20892.
Nakanishi
S
S
Catt
K J
KJ
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology*; D002417:Cattle; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D015398:Signal Transduction; D013324:Strontium / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002412:Cations; D007295:Inositol Phosphates; D000804:Angiotensin II; D001464:Barium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D009543:Nifedipine; D002118:Calcium; D013324:Strontium