Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical trials suggest that synthetic ATP-sensitive K(+) (K(ATP)) channel openers may cause headache and migraine by dilating cerebral and meningeal arteries. We studied the mRNA expression profile of K(ATP) channel subunits in the pig and human middle meningeal artery (MMA) and in the pig middle cerebral artery (MCA). We determined the order of potency of four K(ATP) channel openers when applied to isolated pig MMA and MCA, and we examined the potential inhibitory effects of the Kir6.1 subunit specific K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation of the isolated pig MMA and MCA. Using conventional RT-PCR, we detected the mRNA transcripts of the K(ATP) channel subunits Kir6.1 and SUR2B in all the examined pig and human intracranial arteries. Application of K(ATP) channel openers to isolated pig MMA and MCA in myographs caused a concentration-dependent vasodilatation with an order of potency that supports the presence of functional SUR2B K(ATP) channel subunits. 10(-7) M PNU-37883A significantly inhibited the in vitro dilatory responses of the potent K(ATP) channel opener P-1075 in both pig MMA and MCA. In conclusion, our combined mRNA expression and pharmacological studies indicate that Kir6.1/SUR2B is the major functional K(ATP) channel complex in the pig MMA and MCA, and mRNA expression studies suggest that the human MMA shares this K(ATP) channel subunit profile. Specific blocking of Kir6.1 or SUR2B K(ATP) channel subunits in large cerebral and meningeal arteries may be a future anti-migraine strategy.
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PMID:K ATP channels in pig and human intracranial arteries. 1899 11

K(ATP) channel openers are vasodilators and induce headache in normal subjects. We previously identified the Kir6.1/SUR2B K(ATP) channel subtype in major cerebral and dural arteries of rat, pig and man. We hypothesized that craniovascular Kir6.1/SUR2B K(ATP) channels mediate the headache-inducing effects of K(ATP) channel openers and that a Kir6.1/SUR2B specific blocker might be effective in the treatment of primary headaches such as migraine. Since K(ATP) channels are ubiquitous, we characterized the K(ATP) channel subtypes in major rat cranial and peripheral arteries and organs in order to understand the possible adverse effects of a Kir6.1/SUR2B blocker. We studied the mRNA expression of K(ATP) channel subunits in rat femoral, mesenteric, renal, coronary, basilar, middle cerebral and middle meningeal arteries and in tissue from rat heart, brain, liver, colon, lung, kidney and pancreas. We also studied the effects and potencies of a panel of synthetic K(ATP) channel openers and their potential inhibition by the Kir6.1 subunit-specific K(ATP) channel blocker PNU-37883A in segments of the arteries mounted in a wire myograph. Our studies suggest that Kir6.1/SUR2B forms the major functional K(ATP) channel complex in rat cranial and peripheral arteries. The mRNA transcripts of SUR1 and Kir6.2 subunits were predominantly found in brain, pancreas and heart, while SUR2A mRNA was merely detected within the heart. K(ATP) channel blockers highly specific for the SUR2B subunit may have no adverse CNS and cardiac effects and will not affect insulin release in the pancreas. However, a SUR2B blocker may not discriminate between cranial and peripheral arteries.
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PMID:Presence and vascular pharmacology of KATP channel subtypes in rat central and peripheral tissues. 2036 54