PT  - JOURNAL ARTICLE
AU  - Masanori Haba
AU  - Noboru Hatakeyama
AU  - Hiroyuki Kinoshita
AU  - Hiroki Teramae
AU  - Toshiharu Azma
AU  - Yoshio Hatano
AU  - Naoyuki Matsuda
TI  - The Modulation of Vascular ATP-Sensitive K<sup>+</sup> Channel Function via the Phosphatidylinositol 3-Kinase–Akt Pathway Activated by Phenylephrine
AID  - 10.1124/jpet.110.167775
DP  - 2010 Aug 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 673--678
VI  - 334
IP  - 2
4099  - http://jpet.aspetjournals.org/content/334/2/673.short
4100  - http://jpet.aspetjournals.org/content/334/2/673.full
SO  - J Pharmacol Exp Ther2010 Aug 01; 334
AB  - The present study examined the modulator role of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway activated by the α-1 adrenoceptor agonist phenylephrine in ATP-sensitive K+ channel function in intact vascular smooth muscle. We evaluated the ATP-sensitive K+ channel function and the activity of the PI3K–Akt pathway in the rat thoracic aorta without endothelium. The PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (10−5 M) augmented relaxation in response to the ATP-sensitive K+ channel opener levcromakalim (10−8 to 3 × 10−6 M) in aortic rings contracted with phenylephrine (3 × 10−7 M) but not with 9,11-dideoxy-11α,9α-epoxy-methanoprostaglandin F2α (U46619; 3 × 10−8 M), although those agents induced similar contraction. ATP-sensitive K+ channel currents induced by levcromakalim (10−6 M) in the presence of phenylephrine (3 × 10−7 M) were enhanced by the nonselective α-adrenoceptor antagonist phentolamine (10−7 M) and LY294002 (10−5 M). Levels of the regulatory subunits of PI3K p85-α and p55-γ increased in the membrane fraction from aortas without endothelium treated with phenylephrine (3 × 10−7 M) but not with U46619 (3 × 10−8 M). Phenylephrine simultaneously augmented Akt phosphorylation at Ser473 and Thr308. Therefore, activation of the PI3K–Akt pathway seems to play a role in the impairment of ATP-sensitive K+ channel function in vascular smooth muscle exposed to α-1 adrenergic stimuli.