Calcium and calmodulin regulate atrial natriuretic factor stimulation of cyclic GMP in a human renal cell line.
We examined calcium and calmodulin regulation of atrial natriuretic factor stimulation of particulate-membrane guanylate cyclase (ANF-s-GC) in SK-NEP-1 cells. W7 and trifluoropiperazine, but not W5, inhibited whole cellular ANF-stimulated cyclic GMP accumulation (ANF-s-cGMP). EGTA and LaCl3 decreased ANF-s-GC and calmodulin reversed this inhibition. A23187-induced inhibition of ANF-s-cGMP was only partly reversible by IBMX. H7 or staurosporine counteracted the inhibitory effect of A23187. Calcium inhibited basal and ANF-s-GC. These data suggest that at low concentrations of calcium, ANF-s-GC was calcium-calmodulin dependent but high concentrations of calcium inhibited ANF-s-GC through phosphodiesterase, through inhibition of GC, and probably through protein kinase C.
Alton Ochsner Medical Foundation, New Orleans, LA 70121.
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M
Sekiya
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J
Vaughn
Y
Y
Shigematsu
E D
ED
Frohlich
F E
FE
Cole
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007680:Kidney Neoplasms; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology; D009396:Wilms Tumor
D000470:Alkaloids; D002147:Calmodulin; D007546:Isoquinolines; C472955:NPPA protein, human; D010879:Piperazines; D013449:Sulfonamides; C028521:lanthanum chloride; D014268:Trifluoperazine; D000001:Calcimycin; D008345:Manganese; D004533:Egtazic Acid; C017967:W 7; D007811:Lanthanum; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019311:Staurosporine; D008274:Magnesium; D002118:Calcium