Fauaz G, Feres T, Borges A C, Paiva T B
Department of Biophysics, Escola Paulista de Medicina, Universidade Federal de São Paulo, 04023-062, São Paulo, SP, Brazil.
Br J Pharmacol. 2000 Oct;131(4):788-94. doi: 10.1038/sj.bjp.0703630.
The role of alpha(2)-adrenoceptors in the response of aorta smooth muscle rings to the alpha(2)-adrenoceptors agonists UK 14,304 and clonidine was studied. Stimulation by 1 - 10 nM UK 14,304 caused dose-dependent relaxant responses in BaCl(2)-contracted endothelium-denuded aorta rings, and hyperpolarization in rings with or without endothelium, which were inhibited by yohimbine and glibenclamide, but not affected by prazosin, propranolol, apamin or iberiotoxin. At higher concentrations (10 nM - 10 microM) UK 14,304 also induced a depolarizing effect which was potentiated by yohimbine and inhibited by prazosin. These results indicate that UK 14,304 acts on alpha(2)-adrenoceptors at lower concentrations and on both alpha(1)- and alpha(2)-adrenoceptors above 10 nM. In rings, with or without endothelium, noradrenaline had a depolarizing effect which was inhibited by prazosin. Adrenaline did not affect the membrane potential but in the presence of prazosin caused hyperpolarization, which was inhibited by yohimbine and glibenclamide. These results indicate that noradrenaline is more selective for alpha(1)-, whereas adrenaline has similar affinities for alpha(1)- and alpha(2)-adrenoceptors. In aortae with endothelium, L-NNA caused a small depolarization but did not affect the hyperpolarization induced by UK 14,304, indicating that NO is not involved in that response. Glibenclamide induced a small depolarization in aortae, with or without endothelium, indicating that ATP-sensitive K(+) channels may play a role in maintaining the smooth muscle's membrane potential. Our results indicate that, in rat aorta, alpha(2)-adrenoceptors are also present in the smooth muscle, and that these receptors act through small-conductance ATP-sensitive K(+) channels.
研究了α₂ - 肾上腺素能受体在主动脉平滑肌环对α₂ - 肾上腺素能受体激动剂UK 14,304和可乐定反应中的作用。1 - 10 nM的UK 14,304刺激可使BaCl₂收缩的去内皮主动脉环产生剂量依赖性舒张反应，并使有或无内皮的环发生超极化，这一反应被育亨宾和格列本脲抑制，但不受哌唑嗪、普萘洛尔、蜂毒明肽或iberiotoxin影响。在较高浓度（10 nM - 10 μM）时，UK 14,304还诱导去极化效应，该效应被育亨宾增强，被哌唑嗪抑制。这些结果表明，UK 14,304在较低浓度时作用于α₂ - 肾上腺素能受体，在高于10 nM时作用于α₁ - 和α₂ - 肾上腺素能受体。在有或无内皮的环中，去甲肾上腺素具有去极化作用，被哌唑嗪抑制。肾上腺素不影响膜电位，但在哌唑嗪存在时引起超极化，这一反应被育亨宾和格列本脲抑制。这些结果表明，去甲肾上腺素对α₁ - 肾上腺素能受体更具选择性，而肾上腺素对α₁ - 和α₂ - 肾上腺素能受体具有相似的亲和力。在有内皮的主动脉中，L - NNA引起轻微去极化，但不影响UK 14,304诱导的超极化，表明NO不参与该反应。格列本脲在有或无内皮的主动脉中均诱导轻微去极化，表明ATP敏感性钾通道可能在维持平滑肌膜电位中起作用。我们的结果表明，在大鼠主动脉中，α₂ - 肾上腺素能受体也存在于平滑肌中，并且这些受体通过小电导ATP敏感性钾通道发挥作用。
