KATP channel expression and pharmacological in vivo and in vitro studies of the KATP channel blocker PNU-37883A in rat middle meningeal arteries

K. B. Ploug, L. J. Boni, M. Baun, A. Hay-Schmidt, J. Olesen, I. Jansen-Olesen

20 Citationer (Scopus)

Abstract

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+ (KATP) channel opening may cause migraine by dilatating intracranial arteries, including the middle meningeal artery (MMA). We studied the KATP channel expression profile in rat MMA and examined the potential inhibitory effects of the KATP channel blocker PNU-37883A on KATP channel opener-induced relaxation of the rat MMA, using the three KATP channel openers levcromakalim, pinacidil and P-1075. Experimental approach: mRNA and protein expression of KATP 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 KATP 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 KATP 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 KATP channel openers in rat MMA at 10-7 and 3 × 10-7 M. Conclusions and implications: We suggest that Kir6.1/SUR2B is the major functional KATP channel complex in the rat MMA. Furthermore, we demonstrate the potent in vivo and in vitro blocking potentials of PNU-37883A on KATP channel opener-induced relaxation of the rat MMA.

OriginalsprogEngelsk
TidsskriftBritish Journal of Pharmacology
Vol/bind154
Udgave nummer1
Sider (fra-til)72-81
Antal sider10
ISSN0007-1188
DOI
StatusUdgivet - maj 2008
Udgivet eksterntJa

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