Mechanism of neuropeptide Y inhibition of vasopressin action in rat cortical collecting tubule.

Neuropeptide Y (NPY) is a unique 36-amino acid peptide found in high concentrations in brain and peripheral neurons. Although NPY is present in kidney tissue, its role in regulation of renal function has not been delineated. We found that NPY significantly decreases arginine vasopressin (AVP) but not adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated hydraulic conductivity (Lp) in perfused rat cortical collecting tubules (CCT). Either alpha 2-adrenergic receptor blockade (yohimbine) or occupancy (clonidine) prevent NPY inhibition of AVP-stimulated Lp. By contrast, alpha 1-adrenergic receptor blockade with prazosin did not alter NPY inhibition of AVP action. Pretreatment of CCT with pertussis toxin also abolishes NPY inhibition of AVP-stimulated Lp. These data suggest that NPY acts via an alpha 2-adrenergic receptor coupled to a pertussis toxin-sensitive protein to inhibit AVP-stimulated cAMP formation and Lp in the rat CCT.