Disparate effects of neuropeptide Y and clonidine on the excretion of sodium and water in the rat.
Previous studies have demonstrated a similarity between the ability of neuropeptide Y (NPY) and clonidine to inhibit renin release and inhibit cAMP production. We therefore compared the effects of clonidine and NPY on the excretion of sodium and water in anesthetized rats which were unilaterally nephrectomized (right kidney) 10 days prior to the experiment. On the experimental day, rats were anesthetized (nembutal) and the left kidney exposed for the intrarenal infusion of the study drugs. The lowest dose of NPY (0.3 microgram/kg per min) investigated failed to alter renal function. Clonidine (0.3 microgram/kg per min) and NPY (1 microgram/kg per min) produced a similar increase in urine volume. Only NPY increased sodium excretion and osmolar clearance. Free water clearance was only increased by clonidine. Blood pressure and creatinine clearance were similar in all groups investigated. These effects were attenuated by pretreatment with pertussis toxin (5 days). The ability of pertussis toxin to block these effects suggests that the renal effects of NPY and clonidine are coupled to a G protein, conceivably the inhibitory Gi protein of the adenylate cyclase system. The disparate effects on sodium excretion and on free water and osmolar clearance indicate that the effects of these compounds may be mediated through the inhibition of different pools of hormonally stimulated cAMP.
Smyth
D D
DD
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Blandford
D E
DE
Thom
S L
SL
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D008297:Male; D009392:Nephrectomy; D009478:Neuropeptide Y / Q000494:pharmacology*; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010566:Virulence Factors, Bordetella; D012964:Sodium; D003404:Creatinine; D037342:Pertussis Toxin; D003000:Clonidine; D011188:Potassium