Inhibitory effect of Ca(2+) on ATP-mediated stimulation of NPR-A-coupled guanylyl cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats.
Atrial natriuretic peptide (ANP) regulates blood pressure mainly through the occupation of the guanylyl cyclase-coupled receptor NPR-A, which requires ATP interaction for maximal activation. This study investigates the effect of extracellular Ca(2+) on ATP-mediated regulation of NPR-A-coupled guanylyl cyclase activity in glomerular membranes from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). ATP induced a significant increase in basal and ANP(1-28)-stimulated guanylyl cyclase activity that was greater in SHR than in WKY. Extracellular Ca(2+) inhibited ATP-stimulated guanylyl cyclase activity in a concentration-dependent manner, but did not modify basal and ANP(1-28)-stimulated guanylyl cyclase activity. In the presence of ATP, NPR-A showed higher affinity for ANP(1-28) and lower Bmax. Ca(2+) did not modify NPR-A-ANP(1-28) binding properties. The different effects of extracellular Ca(2+) on ANP(1-28)- or ATP-mediated guanylyl cyclase activation suggest that these events are differentially regulated. Addition of extracellular Ca(2+) induced similar effects in hypertensive and normotensive rats, suggesting that it is not responsible for the elevated cGMP production observed in SHR.
Woodard
G E
GE
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA. GeoffreyW@intra.niddk.nih.gov
Zhao
J
J
Rosado
J A
JA
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000378:metabolism; D007700:Kinetics; D023421:Models, Animal; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*
D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; D002118:Calcium