Neuropeptide Y and its receptor analogs differentially modulate the immunoreactivity for neuronal or endothelial nitric oxide synthase in the rat brain following focal ischemia with reperfusion.
An intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY) or [Leu31, Pro34]-NPY (non-Y2 receptor agonist) given during middle cerebral artery occlusion (MCAO) increases the infarct volume and nitric oxide (NO) overproduction in the rat brain. An i.c.v. injection of NPY3-36 (non-Y1 receptor agonist) has no effects, while BIBP3226 (selective Y1 receptor antagonist) reduces the infarct volume and NO overproduction. This study examined the effects of NPY or its receptor analog on the immunoreactivity (ir) for three isoforms of NO synthase (NOS) following 1 h of MCAO and 3 h of reperfusion. Focal ischemia/reperfusion led to increased ir for neuronal NOS (nNOS) within the ipsilateral caudate putamen and insular cortex. NPY or [Leu31, Pro34]-NPY enhanced but BIBP3226 suppressed such increase in the nNOS-ir. Focal ischemia/reperfusion also led to an ipsilateral increase in extent and/or intensity of the ir for endothelial NOS (eNOS) in the caudate putamen and/or parietal cortex. NPY or [Leu31, Pro34]-NPY suppressed but BIBP3226 enhanced such change in the eNOS-ir. NPY3-36 did not consistently influence the nNOS-ir or eNOS-ir following MCAO. Specific ir for inducible NOS was undetectable. These opposing effects of NPY-Y1 receptor activation or inhibition on nNOS and eNOS may lead to harmful or beneficial consequences following ischemia/reperfusion.
Chen
Shao Hua
SH
Division of Neurology, University Department of Medicine, Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
Cheung
Raymond Tak Fai
RT
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology*; D002536:Cerebral Arteries / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D015427:Reperfusion Injury; D013696:Temperature; D013997:Time Factors
D014151:Anti-Anxiety Agents; C092926:BIBP 3226; D009478:Neuropeptide Y; D020033:Protein Isoforms; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat