Increased cortical expression of the orexin-1 receptor following permanent middle cerebral artery occlusion in the rat.
The orexins (hypocretins) have recently been implicated in neurodegeneration associated with narcolepsy. Therefore, the current study was designed to investigate changes in the expression of prepro-orexin and the orexin receptors, OX1R and OX2R following permanent middle cerebral artery occlusion (MCAO) in the rat. Six and twenty-four hours following MCAO, increased OX1R mRNA and protein expression (as assessed by Western blotting and immunohistochemistry) was detected in the ischaemic cortex compared with control tissue. In contrast, however, no increase in OX2R mRNA was detected at any time-point and prepro-orexin levels in the cortex were below assay detection levels. This study shows that orexin receptor localization is altered following cerebral ischaemia. The development of selective orexin receptor antagonists will be crucial in establishing a role for this family of novel peptides in the mechanisms underlying ischaemic cell death.
Irving
E A
EA
Neurology CEDD, GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (N) H25/119, Harlow, Essex, CM19 5AW, UK. elaine_a_irving@gsk.com
Harrison
D C
DC
Babbs
A J
AJ
Mayes
A C
AC
Campbell
C A
CA
Hunter
A J
AJ
Upton
N
N
Parsons
A A
AA
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002352:Carrier Proteins / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D064446:Orexin Receptors; D000068797:Orexins; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*
D002352:Carrier Proteins; C578627:Hcrtr1 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D011498:Protein Precursors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide