Neuropeptide Y stimulates renal prostaglandin synthesis in the isolated rat kidney: contribution of Ca++ and calmodulin.
We have investigated the effects of neuropeptide Y (NPY) on vascular tone and renal output of prostaglandins (PGs) and the mechanism underlying these actions by examining the effects of Ca++ depletion, Ca++ channel blockers and calmodulin inhibitors in the isolated Tyrode's perfused rat kidney. Administration of NPY (0.23-2.3 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF1 alpha, the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (60 microM) or nifedipine (1.4 microM), to the perfusion fluid abolished the effects of NPY to promote renal vasoconstriction and PG synthesis. Infusion of calmodulin inhibitors, trifluoperazine (2 microM), W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] (20 microM) or calmidazolium (0.2 microM), attenuated the renal vasoconstriction and the increase in PG output produced by NPY (0.7 nmol). In kidneys perfused with normal Tyrode's solution, infusion of NPY, in a concentration (1.7 X 10(-8) M) that produced only a small transient increase in renal vascular tone and failed to alter the renal output of PGs, enhanced the rise in PGE2 and 6-keto-PGF1 alpha elicited by norepinephrine (0.25 nmol) but not by arginine vasopressin (0.004 nmol) or angiotensin II (0.09 nmol). The renal vasoconstriction elicited by norepinephrine and arginine vasopressin as well as by angiotensin II was enhanced by NPY.(ABSTRACT TRUNCATED AT 250 WORDS)
el Din
M M
MM
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis.
Malik
K U
KU
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D002147:Calmodulin; D009478:Neuropeptide Y; D011453:Prostaglandins; D014268:Trifluoperazine; D015121:6-Ketoprostaglandin F1 alpha; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine