Receptor subtypes Y1 and Y5 are involved in the renal effects of neuropeptide Y

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Abstract
Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and composition are mediated by distinct NPY receptor subtypes. NPY and its analogues, peptide YY (PYY), [Leu31, Pro34]NPY and NPY1336, were infused in incremental doses of 0.3, 1 and 3 μg kg−1 min−1 for 45 min each and the results compared to those obtained in vehicle-infused rats. Renal blood flow was monitored in 15 min intervals, while urine excretion and composition were determined in 15 min collection periods. Plasma renin activity and aldosterone concentrations were measured at the end of the final infusion period. Relative to vehicle NPY, PYY and [Leu31, Pro34]NPY dose-dependently reduced renal blood flow and increased diuresis, natriuresis and calciuresis with roughly similar potency; NPY1336 slightly but significantly increased renal blood flow but had no effect on diuresis, natriuresis and calciuresis. None of the peptides significantly affected endogenous creatinine clearance or kaliuresis. Plasma renin activity was significantly reduced by PYY. Quantitatively similar reductions were observed with NPY and [Leu31, Pro34]NPY but failed to reach statistical significance with the given number of experiments. NPY1336 did not reduce plasma renin activity. None of the peptides significantly affected plasma aldosterone concentrations. In another series of experiments infusion of PYY336 (2 μg kg−1 min−1 for 120 min) did not reduce renal blood flow but significantly enhancd diuresis and natriuresis to a similar extent as the NPY 2 μg kg−1 min−1. In a final series of experiments the Y1-selective antagonist, BIBP 3226 (1 or 10 μg kg−1 min−1) dose-dependently antagonized reductions of renal blood flow elicited by bolus injections of NPY (0.130 μg kg−1). BIBP 3226 (10 μg kg−1 min−1) also inhibited the effects of a 120 min infusion of NPY (2 μg kg−1 min−1) on renal blood flow but had only minor inhibitory effects on enhancements of diuresis and did not significantly affect enhancements of natriuresis. We conclude that NPY reduces renal blood via a classical Y1 subtype of NPY receptor. In contrast enhancements of diuresis, natriuresis and calciuresis occur via a distinct subtype which resembles the receptor that mediates NPY-induced enhancement of food intake. British Journal of Pharmacology (1997) 120, 1335–1343; doi:10.1038/sj.bjp.0701028