K-ATP channel expression and pharmacological in vivo and in vitro studies of the K-ATP channel blocker PNU-37883A in rat middle meningeal arteries
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Background and purpose: Dilatation of cerebral and dural arteries causes a throbbing, migraine-like pain, indicating that these structures are involved in migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K+ (K-ATP) channel opening may cause migraine by dilatating intracranial arteries, including the middle meningeal artery (MMA). We studied the K-ATP channel expression profile in rat MMA and examined the potential inhibitory effects of the K-ATP channel blocker PNU-37883A on K-ATP channel opener-induced relaxation of the rat MMA, using the three K-ATP channel openers levcromakalim, pinacidil and P-1075. Experimental approach: mRNA and protein expression of K-ATP channel subunits in the rat MMA were studied by quantitative real-time PCR and western blotting, respectively. The in vivo and in vitro effects of the K-ATP channel drugs on rat MMA were studied in the genuine closed cranial window model and in myograph baths, respectively. Key results: Expression studies indicate that inwardly rectifying K+ (Kir)6.1/sulphonylurea receptor (SUR) 2B is the major K-ATP channel complex in rat MMA. PNU-37883A (0.5 mg kg(-1)) significantly inhibited the in vivo dilatory effect of levcromakalim (0.025 mg kg(-1)), pinacidil (0.38 mg kg(-1)) and P-1075 (0.016 mg kg(-1)) in rat MMA. In vitro PNU-37883A significantly inhibited the dilatory responses of the three K-ATP channel openers in rat MMA at 10(-7) and 3 x 10(-7) M. Conclusions and implications: We suggest that Kir6.1/SUR2B is the major functional K-ATP channel complex in the rat MMA. Furthermore, we demonstrate the potent in vivo and in vitro blocking potentials of PNU-37883A on K-ATP channel opener-induced relaxation of the rat MMA
Udgivelsesdato: 2008/5
Udgivelsesdato: 2008/5
Originalsprog | Engelsk |
---|---|
Tidsskrift | British Journal of Pharmacology |
Vol/bind | 154 |
Udgave nummer | 1 |
Sider (fra-til) | 72-81 |
Antal sider | 9 |
ISSN | 0007-1188 |
Status | Udgivet - 2008 |
Bibliografisk note
Times Cited: 0ArticleEnglishPloug, K. BUniv Copenhagen, Dept Neurol, Glostrup Res Inst, Fac Hlth Sci,Glostrup Hosp, Nordre Ringvej 69, DK-2600 Glostrup, DenmarkCited References Count: 43293ZTNATURE PUBLISHING GROUPMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLANDLONDON
ID: 10449984