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Inhibitory effect of Ca2+ on ATP-mediated stimulation of NPR-A-coupled guanylyl cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats

100%

Woodard G. E., Zhao J., Rosado J. A.

Journal of Physiology and Pharmacology

2006

tom 57

nr 3

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 Ca2+ 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 ANP1-28-stimulated guanylyl cyclase activity that was greater in SHR than in WKY. Extracellular Ca2+ inhibited ATP-stimulated guanylyl cyclase activity in a concentration-dependent manner, but did not modify basal and ANP1-28-stimulated guanylyl cyclase activity. In the presence of ATP, NPR-A showed higher affinity for ANP1-28 and lower Bmax. Ca2+ did not modify NPR-A-ANP1-28 binding properties. The different effects of extracellular Ca2+ on ANP1-28- or ATP-mediated guanylyl cyclase activation suggest that these events are differentially regulated. Addition of extracellular Ca2+ induced similar effects in hypertensive and normotensive rats, suggesting that it is not responsible for the elevated cGMP production observed in SHR.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Rosado J. A.

1 Woodard G. E.

1 Zhao J.

1 2006

Wyniki wyszukiwania

Inhibitory effect of Ca2+ on ATP-mediated stimulation of NPR-A-coupled guanylyl cyclase in renal glomeruli from spontaneously hypertensive and normotensive rats