The opposing effects of calmodulin, adenosine 5 prime -triphosphate, and pertussis toxin on phorbol ester induced inhibition of atrial natriuretic factor stimulated guanylate cyclase in SK-NEP-1 cells
- Alton Ochsner Medical Foundation, New Orleans, LA (USA)
In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. Calmodulin reversed this inhibition in a dose dependent manner. ATP potentiated Mg++ but not Mn++ supported guanylate cyclase activity. In PMA treated membranes, ATP potentiating effects were abolished. PMA also inhibited ANF-stimulated cGMP accumulation, but pretreatment with PT prevented this PMA inhibition. PT did not affect basal or ANF-stimulated cGMP accumulation. In conclusion, these results demonstrated that PMA inhibited ANF stimulation of particulate guanylate cyclase in opposition to the activating effects of calmodulin or ATP in SK-NEP-1 cells. The protein kinase C inhibitory effects appeared to be mediated via a PT-sensitive G protein.
- OSTI ID:
- 6055496
- Journal Information:
- Life Sciences; (USA), Journal Name: Life Sciences; (USA) Vol. 48:11; ISSN 0024-3205; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKALINE EARTH METAL COMPOUNDS
ANIMAL CELLS
ANIMALS
ANTIGENS
ATP
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BODY
CALMODULIN
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
CYCLASES
ENZYME ACTIVITY
ENZYMES
ESTERS
INHIBITION
KIDNEYS
LYASES
MAGNESIUM COMPOUNDS
MAMMALS
MAN
MANGANESE COMPOUNDS
MATERIALS
MEMBRANES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
PHORBOL ESTERS
PRIMATES
PROTEINS
SYNTHESIS
TOXIC MATERIALS
TOXINS
TRANSITION ELEMENT COMPOUNDS
VERTEBRATES