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Title: 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

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.
Authors:
; ;  [1]
  1. (Alton Ochsner Medical Foundation, New Orleans, LA (USA))
Publication Date:
OSTI Identifier:
6055496
Resource Type:
Journal Article
Resource Relation:
Journal Name: Life Sciences; (USA); Journal Volume: 48:11
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; ATP; BIOLOGICAL EFFECTS; CALMODULIN; CYCLASES; ENZYME ACTIVITY; PHORBOL ESTERS; TOXINS; ANIMAL CELLS; BIOSYNTHESIS; CELL MEMBRANES; INHIBITION; KIDNEYS; MAGNESIUM COMPOUNDS; MAN; MANGANESE COMPOUNDS; NUCLEOTIDES; ALKALINE EARTH METAL COMPOUNDS; ANIMALS; ANTIGENS; BODY; CARCINOGENS; CELL CONSTITUENTS; ENZYMES; ESTERS; LYASES; MAMMALS; MATERIALS; MEMBRANES; ORGANIC COMPOUNDS; ORGANS; PRIMATES; PROTEINS; SYNTHESIS; TOXIC MATERIALS; TRANSITION ELEMENT COMPOUNDS; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology