Bieger Detlef, Parai Kakoli, Ford Carol Ann, Tabrizchi Reza
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Naunyn Schmiedebergs Arch Pharmacol. 2006 Jun;373(3):186-96. doi: 10.1007/s00210-006-0060-7. Epub 2006 Apr 25.
The effect of isoprenaline on tone, cyclic adenosine 3':5' monophosphate (cAMP), and smooth muscle membrane potential (E ( m )) were assessed in rat isolated pulmonary arteries. N(omega)-nitro-L-arginine methyl ester (10.0 microM) or removal of endothelium partially inhibited relaxant responses to isoprenaline, but glibenclamide (10.0 microM) and indomethacin (10.0 microM) did not. While Rp-8-Br-cAMP (30.0 microM), tetraethylammonium (0.3 & 1.0 mM), 4-aminopyridine (100 microM), anandamide (10.0 microM), charybdotoxin (0.1 microM), ouabain (100 microM), and barium chloride (100 microM), incompletely blocked relaxation to isoprenaline, cyclopiazonic acid (1.0 microM), apamin (3.0 microM) and zinc acetate (300 microM) were without effect. Increasing extracellular K(+) (K(+)) inhibited relaxant responses to isoprenaline, completely abolishing the response at 30 mM K+. Vasorelaxant effects of isoprenaline were significantly attenuated in buffer pH 6.4, and concomitant presence of Rp-8-Br-cAMP (30.0 microM) in pH 6.4 produced significant additive inhibition when compared to pH 6.4 without Rp-8-Br-cAMP. Isoprenaline increased cAMP turnover (1.55+/-0.24 fold; mean +/- SEM), which was inhibited by propranolol (1.0 microM). Resting E ( m ) of smooth muscle cells was -63.0+/-0.50 mV, and isoprenaline (1.0 microM) produced hyperpolarisation (-73.3+/-0.80 mV). While glibenclamide failed to affect isoprenaline-induced hyperpolarisation, ICI 118,551 (1.0 microM), anandamide or buffer pH 6.4 prevented it, and barium chloride and oubain combined caused partial inhibition. Isoprenaline-mediated relaxation seems to arise from several processes, including the generation of nitric oxide, the cAMP-cascade and, more importantly, a hyperpolarisation that is not due to activation of ATP-sensitive K channels but possibly of two-pore domain K channels of the TASK family.
在大鼠离体肺动脉中评估了异丙肾上腺素对张力、环磷酸腺苷（cAMP）和平滑肌膜电位（Em）的影响。N（ω）-硝基-L-精氨酸甲酯（10.0微摩尔）或去除内皮部分抑制了对异丙肾上腺素的舒张反应，但格列本脲（10.0微摩尔）和吲哚美辛（10.0微摩尔）则无此作用。虽然Rp-8-溴-cAMP（30.0微摩尔）、四乙铵（0.3和1.0毫摩尔）、4-氨基吡啶（100微摩尔）、花生四烯酸乙醇胺（10.0微摩尔）、大蝎毒素（0.1微摩尔）、哇巴因（100微摩尔）和氯化钡（100微摩尔）不完全阻断对异丙肾上腺素的舒张作用，但环匹阿尼酸（1.0微摩尔）、蜂毒明肽（3.0微摩尔）和醋酸锌（300微摩尔）则无作用。增加细胞外钾离子浓度（[K⁺]e）抑制了对异丙肾上腺素的舒张反应，在30毫摩尔[K⁺]e时完全消除了该反应。在缓冲液pH 6.4中，异丙肾上腺素的血管舒张作用显著减弱，与无Rp-8-溴-cAMP的pH 6.4相比，pH 6.4中同时存在Rp-8-溴-cAMP（30.0微摩尔）产生了显著的相加抑制作用。异丙肾上腺素增加了cAMP周转率（1.55±0.24倍；平均值±标准误），这被普萘洛尔（1.0微摩尔）抑制。平滑肌细胞的静息Em为-63.0±0.50毫伏，异丙肾上腺素（1.0微摩尔）产生超极化（-73.3±0.80毫伏）。虽然格列本脲未能影响异丙肾上腺素诱导的超极化，但ICI 118,551（1.0微摩尔）、花生四烯酸乙醇胺或缓冲液pH 6.4可阻止其发生，氯化钡和哇巴因联合使用可产生部分抑制作用。异丙肾上腺素介导的舒张似乎源于多个过程，包括一氧化氮的生成、cAMP级联反应，更重要的是一种超极化，其并非由ATP敏感性钾通道的激活引起，而是可能由TASK家族的双孔域钾通道引起。
