Characterization of vascular postsynaptic neuropeptide Y receptor function and regulation. 1. NPY-induced constriction in isolated rat femoral artery rings is mediated by both Y1 and Y2 receptors: evidence from benextramine protection studies.
Neuropeptide Y (NPY), a potent pressor agent and vasoconstrictor, is thought to contribute to the sympathetically mediated postsynaptic regulation of blood pressure primarily through activation of vascular Y1 rather than Y2 NPY receptors. However, data are available that conflict with this conclusion. In this article, the relative roles of postsynaptic Y1 and Y2 receptors as mediators of direct NPY-induced isolated rat femoral artery ring vasoconstriction were evaluated through use of selective Y1 and Y2 agonists, [Leu31, Pro34]NPY ([Leu, Pro]NPY) and NPY13-36 [NPY(13-36)], respectively, and the NPY receptor antagonist benextramine (BXT). NPY, [Leu, Pro]NPY and NPY(13-36) were equipotent as vasoconstrictors, and constriction induced by each peptide, but not by the calcium channel agonist BAY K 8644 (BAY), was almost completely blocked by 10 microM BXT. Each of the three peptides also induced self- and cross-desensitization and protection from BXT blockade, except that [Leu, Pro]NPY neither desensitized nor protected NPY(13-36)-associated responses. NPY also failed to protect [Leu, Pro]NPY- and NPY(13-36)-elicited constriction, and NPY(13-36) failed to provide self-protection, from BXT blockade. However, in these instances, as opposed to the [Leu, Pro]NPY-NPY(13-36) cross-protection experiments, the occurrence of protection was probably masked by the relatively large magnitude of desensitization concurrently induced by the protecting peptide. Taken together, the present findings suggest that NPY-induced rat femoral artery vasoconstriction is mediated by separate, BXT-sensitive, postsynaptic Y1 ([Leu, Pro]NPY-activated) and Y2 [NPY(13-36)-activated] receptors.
Tessel
R E
RE
Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence.
Miller
D W
DW
Misse
G A
GA
Dong
X
X
Doughty
M B
MB
D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004336:Drug Antagonism; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000145:classification / Q000502:physiology*; D013569:Synapses; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C029998:benextramine; D003538:Cystamine