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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
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- 1 - 10 (10page)
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Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous,gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated Kþ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes.
Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2þ-activated Kþ, inward rectifier Kþ and ATP-sensitive Kþ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2þ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, a-methyl 5-HT, a 5-HT2receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.
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참고문헌 (23)
참고문헌 신청
Albert AP / 1996 / The effect of 5-HT and selective 5-HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro / Br J Pharmacol 119 : 519 ~ 52
Alexander N / 2009 / Geneenvironment interactions predict cortisol responses after acute stress: implications for the etiology of depression / Psychoneuroendocrinology 34 :
Bae YM / 2006 / Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated Kþ currents / Biochem Biophys Res Commun 347 : 46
Barbey JT / 1998 / SSRI safety in overdose / J Clin Psychiatry 59 : 42 ~ 48
Berg KA / 2008 / Physiological and therapeutic relevance of constitutive activity of 5-HT 2A and 5-HT 2C receptors for the treatment of depression / Prog Brain Res 172 : 287
Alexander N / 2009 / Geneenvironment interactions predict cortisol responses after acute stress: implications for the etiology of depression / Psychoneuroendocrinology 34 :
Bae YM / 2006 / Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated Kþ currents / Biochem Biophys Res Commun 347 : 46
Barbey JT / 1998 / SSRI safety in overdose / J Clin Psychiatry 59 : 42 ~ 48
Berg KA / 2008 / Physiological and therapeutic relevance of constitutive activity of 5-HT 2A and 5-HT 2C receptors for the treatment of depression / Prog Brain Res 172 : 287
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