title: Neuropeptide Y bioavailability is suppressed in the hindlimb of female Sprague-Dawley rats.
abstract: We recently reported that male, but not female, rats exhibit basal endogenous neuropeptide Y Y(1)-receptor modulation of hindlimb vasculature. The lack of baseline endo-genous Y(1)-receptor control in females was evident despite the expression of Y(1)-receptors and neuropeptide Y in hindlimb skeletal muscle tissue. The following study addressed the hypothesis that neuropeptide Y bioavailability is blunted in female rats under baseline conditions. It was further hypothesized that enhanced prejunctional autoinhibitory neuropeptide Y Y(2)-receptor expression and/or proteolytic processing of released neuropeptide Y may persist in female rats. Using western blot analysis, it was observed that females had greater overall neuropeptide Y Y(2)-receptor expression in skeletal muscle compared to males (P < 0.05). To address the prevalence/impact of baseline endogenous Y(2)-receptor activation on neuropeptide Y release in hindlimb vasculature, an arterial infusion of BIIE0246 (specific non-peptide Y(2)-receptor antagonist; 170 microg kg(-1)) was carried out on female and male rats. Y(2)-receptor blockade resulted in a decrease in hindlimb vascular conductance in females and males (P < 0.05). However, the BIIE0246-induced decrease in vascular conductance was Y(1)-receptor dependent in females, but not males (P < 0.05). In addition, compared to baseline, BIIE0246 infusion resulted in increased plasma neuropeptide Y concentration in females (P < 0.05), while there was no observable change in males. In a final experiment, systemic inhibition of proteolytic enzymes dipeptidylpeptidase IV (via 500 nM diprotin A) and aminopeptidase P (via 180 nM 2-mercaptoethanol) elicited a Y(1)-receptor-dependent decrease in hindlimb vascular conductance in females (P < 0.05). It was concluded that our previously reported lack of basal endogenous Y(1)-receptor activation in female hindlimb vasculature was (at least partially) due to prejunctional Y(2)-receptor autoinhibition and proteolytic processing of neuropeptide Y.
authors.affiliation: Neurovascular Research Laboratory, School of Kinesiology, University of Western Ontario, London, Canada.
authors.forename: Dwayne N
authors.initials: DN
authors.lastname: Jackson
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Milne
authors.forename: Earl G
authors.initials: EG
authors.lastname: Noble
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Shoemaker
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D008623:Mercaptoethanol / Q000008:administration & dosage / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D001552:Benzazepines; D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D009842:Oligopeptides; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D008623:Mercaptoethanol; C041445:diprotin A; D001120:Arginine; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; C403256:BIIE 0246