K ATP channels in pig and human intracranial arteries

Kenneth Beri Ploug; Mette Aaskov Sørensen; Lotte Strøbech; Dan Arne Klaerke; Anders Hay-Schmidt; Majid Sheykhzade; Jes Olesen; Inger Jansen-Olesen; Kenneth Beri Ploug; Mette Aaskov Sørensen; Lotte Bjørg Strøbech; Dan Arne Klærke; Anders Hay-Schmidt; Majid Sheykhzade; Jes Olesen; Inger Jansen-Olesen

doi:10.1016/j.ejphar.2008.10.041

K ATP channels in pig and human intracranial arteries

Kenneth Beri Ploug, Mette Aaskov Sørensen, Lotte Strøbech, Dan Arne Klaerke, Anders Hay-Schmidt, Majid Sheykhzade, Jes Olesen, Inger Jansen-Olesen, Kenneth Beri Ploug, Mette Aaskov Sørensen, Lotte Bjørg Strøbech, Dan Arne Klærke, Anders Hay-Schmidt, Majid Sheykhzade, Jes Olesen, Inger Jansen-Olesen

16 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	European Journal of Clinical Pharmacology
Vol/bind	601
Udgave nummer	1-3
Sider (fra-til)	43-9
Antal sider	6
ISSN	0031-6970
DOI	https://doi.org/10.1016/j.ejphar.2008.10.041 https://doi.org/10.1016/j.ejphar.2008.10.041
Status	Udgivet - 2008

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Ploug, K. B., Sørensen, M. A., Strøbech, L., Klaerke, D. A., Hay-Schmidt, A., Sheykhzade, M., Olesen, J., Jansen-Olesen, I., Ploug, K. B., Sørensen, M. A., Strøbech, L. B., Klærke, D. A., Hay-Schmidt, A., Sheykhzade, M., Olesen, J., & Jansen-Olesen, I. (2008). K ATP channels in pig and human intracranial arteries. European Journal of Clinical Pharmacology, 601(1-3), 43-9. https://doi.org/10.1016/j.ejphar.2008.10.041, https://doi.org/10.1016/j.ejphar.2008.10.041

Ploug, KB, Sørensen, MA, Strøbech, L, Klaerke, DA , Hay-Schmidt, A , Sheykhzade, M , Olesen, J, Jansen-Olesen, I, Ploug, KB, Sørensen, MA, Strøbech, LB, Klærke, DA, Hay-Schmidt, A, Sheykhzade, M, Olesen, J & Jansen-Olesen, I 2008, 'K ATP channels in pig and human intracranial arteries', European Journal of Clinical Pharmacology, bind 601, nr. 1-3, s. 43-9. https://doi.org/10.1016/j.ejphar.2008.10.041, https://doi.org/10.1016/j.ejphar.2008.10.041

@article{524e0690a92a11df928f000ea68e967b,

title = "K ATP channels in pig and human intracranial arteries",

abstract = "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.",

author = "Ploug, {Kenneth Beri} and S{\o}rensen, {Mette Aaskov} and Lotte Str{\o}bech and Klaerke, {Dan Arne} and Anders Hay-Schmidt and Majid Sheykhzade and Jes Olesen and Inger Jansen-Olesen and Ploug, {Kenneth Beri} and S{\o}rensen, {Mette Aaskov} and Str{\o}bech, {Lotte Bj{\o}rg} and Kl{\ae}rke, {Dan Arne} and Anders Hay-Schmidt and Majid Sheykhzade and Jes Olesen and Inger Jansen-Olesen",

note = "Keywords: ATP-Binding Cassette Transporters; Adamantane; Animals; Cerebral Arteries; Gene Expression; Humans; KATP Channels; Male; Meningeal Arteries; Middle Aged; Morpholines; Potassium Channel Blockers; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Receptors, Drug; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Swine",

year = "2008",

doi = "10.1016/j.ejphar.2008.10.041",

language = "English",

volume = "601",

pages = "43--9",

journal = "European Journal of Clinical Pharmacology",

issn = "0031-6970",

publisher = "Springer",

number = "1-3",

}

TY - JOUR

T1 - K ATP channels in pig and human intracranial arteries

AU - Ploug, Kenneth Beri

AU - Sørensen, Mette Aaskov

AU - Strøbech, Lotte

AU - Klaerke, Dan Arne

AU - Hay-Schmidt, Anders

AU - Sheykhzade, Majid

AU - Olesen, Jes

AU - Jansen-Olesen, Inger

AU - Ploug, Kenneth Beri

AU - Sørensen, Mette Aaskov

AU - Strøbech, Lotte Bjørg

AU - Klærke, Dan Arne

AU - Hay-Schmidt, Anders

AU - Sheykhzade, Majid

AU - Olesen, Jes

AU - Jansen-Olesen, Inger

N1 - Keywords: ATP-Binding Cassette Transporters; Adamantane; Animals; Cerebral Arteries; Gene Expression; Humans; KATP Channels; Male; Meningeal Arteries; Middle Aged; Morpholines; Potassium Channel Blockers; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Receptors, Drug; Reverse Transcriptase Polymerase Chain Reaction; Species Specificity; Swine

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.ejphar.2008.10.041

DO - 10.1016/j.ejphar.2008.10.041

M3 - Journal article

C2 - 18996111

SN - 0031-6970

VL - 601

SP - 43

EP - 49

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

IS - 1-3

ER -

K ATP channels in pig and human intracranial arteries

Abstract

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