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Different effect of ATP on ANP receptor guanylyl cyclase in spontaneously hypertensive and normotensive rats
Author(s) -
Woodard G. E.,
Zhao J.,
Rosado J. A.
Publication year - 2006
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/j.1748-1716.2006.01628.x
Subject(s) - medicine , atrial natriuretic peptide , endocrinology , receptor , chemistry , stimulation , basal (medicine) , endogeny , biology , insulin
Aim: Natriuretic peptide receptor A (NPR‐A) is the main physiological receptor for atrial natriuretic peptide (ANP). Maximal activation of NPR‐A guanylyl cyclase (GC) requires ANP binding and ATP interaction with a putative cytoplasmic site. This study investigates the regulatory effect of ATP on GC‐coupled NPR‐A activity in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Methods: Cyclic GMP production and competitive inhibition of [ 125 I]ANP 1−28 binding were performed in solubilized glomerular and papillary renal membranes. Results: Here, we report that incubation of renal glomerular and papillary membranes with ATP induced a concentration‐dependent increase in basal and ANP 1−28 ‐stimulated GC activity that was significantly greater in SHR than in age‐matched WKY. ATP γ S was more effective than ATP and induced a greater stimulation of cGMP production in SHR than in WKY. In contrast, in solubilized membranes ATP exerted an inhibitory role on basal and ANP 1−28 ‐induced GC activity, suggesting that an accessory protein is required for ATP‐induced GC activation. ATP increases NPR‐A affinity for ANP 1−28 and decreased B max in crude and solubilized membranes. Kinetic analysis of GC‐coupled NPR‐A revealed that ATP reduced the Km and increased the V max , an effect that was greater in SHR. Conclusion: Our observations indicate that ATP exerts a greater net effect on NPR‐A in SHR than in WKY, which might explain the greater rate of cGMP production observed in SHR compared to WKY.