Possible location and function of neuropeptide Y receptor subtypes in the rat mesenteric arterial bed.
Earlier investigation of the vascular actions of Neuropeptide Y (NPY) led us to propose that distinct receptors mediated the prejunctional inhibition of periarterial nerve-stimulated norepinephrine (NE) release and the postjunctional potentiation of the increase in perfusion pressure elicited by vasoconstrictors. These receptors were designated Y2 and Y1, respectively, based on the ability of C-terminal fragments to mimic the former action. The present study investigates further the involvement of these putative receptor subtypes in the isolated and perfused mesenteric arterial bed. [Leu31Pro34]NPY, a novel analog with specificity at the Y1 receptors, potentiated the increase in perfusion pressure elicited by exogenously administered NE and arginine vasopressin, confirming the existence of this NPY subtype postjunctionally. This immediate and prolonged potentiation was abolished by phentolamine, attenuated by benextramine and the reputed NPY antagonist, PYX1. [11-36]NPY also produced a concentration-dependent potentiation of NE-stimulated increase in perfusion pressure suggesting that the Y2 receptor subtype may also be present postjunctionally in this model of the vascular neuroeffector junction. The finding that the profile of this potentiation differed from that elicited by [Leu31Pro34]NPY and, in contrast to the latter, was not attenuated by PYX1, intimates the existence of both distinct subtypes postjunctionally. [Leu31Pro34]NPY also reduced periarterial nerve-stimulated release of NE with a concomitant reduction in perfusion pressure indicating, in addition to the Y2 subtype, the presence of the Y1 receptor prejunctionally in the rat mesenteric arterial bed.
Department of Pharmacological and Physiological Science, Saint Louis University Medical Center, Missouri.
M A
MA
McAuley
T C
TC
Westfall
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000145:classification / Q000187:drug effects* / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; C029998:benextramine; D003538:Cystamine; D009638:Norepinephrine; D010646:Phentolamine