Ellershaw D C, Greenwood I A, Large W A
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
J Physiol. 2002 Jul 15;542(Pt 2):537-47. doi: 10.1113/jphysiol.2002.018770.
The effect of noradrenaline on the volume-sensitive chloride current (I(Cl(swell))) was studied with conventional whole-cell recording techniques in freshly dispersed isolated smooth muscle cells of the rabbit portal vein. In the absence of receptor antagonists, noradrenaline produced an increase in the amplitude of I(Cl(swell)) in some cells and a decrease in others. In the presence of the beta-adrenoceptor antagonist propranolol, noradrenaline increased I(Cl(swell)) and in the presence of the alpha(1)-adrenoceptor antagonist prazosin, noradrenaline reduced I(Cl(swell).) The phospholipase C (PLC) inhibitor U73122 reduced the amplitude of I(Cl(swell)) whereas the inactive analogue U73343 had no effect. The phorbol esters phorbol-12-myristate-13-acetate (PMA) and phorbol-12,13-dibutyrate (PDBu) increased the amplitude of I(Cl(swell)) by approximately 60 and 100 %, respectively, in a voltage-independent fashion. Inhibitors of protein kinase C (PKC) chelerythrine and calphostin-C decreased the amplitude of I(Cl(swell)) in a concentration-dependent but voltage-independent manner. Bath application of 8-Br-cAMP decreased I(Cl(swell)) by about 60 % whereas the inhibitor of protein kinase A (PKA) KT5720 increased the amplitude of I(Cl(swell)) by approximately 80-90 %. In the presence of propranolol, chelerythrine prevented the increase of I(Cl(swell)) by noradrenaline; in the presence of prazosin, KT5720 blocked the inhibitory action of noradrenaline. The results show that in rabbit portal vein myocytes noradrenaline enhances I(Cl(swell)) by acting on alpha(1)-adrenoceptors and reduces I(Cl(swell)) by stimulating beta-adrenoceptors. The data suggest that the potentiating and inhibitory effects of noradrenaline are mediated, respectively, by PKC and PKA.
采用传统的全细胞记录技术，在新鲜分离的兔门静脉平滑肌细胞中研究了去甲肾上腺素对容积敏感性氯电流（I(Cl(swell))）的影响。在不存在受体拮抗剂的情况下，去甲肾上腺素在一些细胞中使I(Cl(swell))的幅度增加，而在另一些细胞中使其降低。在存在β-肾上腺素能受体拮抗剂普萘洛尔的情况下，去甲肾上腺素增加I(Cl(swell))；在存在α(1)-肾上腺素能受体拮抗剂哌唑嗪的情况下，去甲肾上腺素降低I(Cl(swell))。磷脂酶C（PLC）抑制剂U73122降低I(Cl(swell))的幅度，而无活性类似物U73343则无作用。佛波酯佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA）和佛波醇-12,13-二丁酸酯（PDBu）以电压非依赖性方式分别使I(Cl(swell))的幅度增加约60%和100%。蛋白激酶C（PKC）抑制剂白屈菜红碱和钙泊三醇以浓度依赖性但电压非依赖性方式降低I(Cl(swell))的幅度。浴槽应用8-溴-cAMP使I(Cl(swell))降低约60%，而蛋白激酶A（PKA）抑制剂KT5720使I(Cl(swell))的幅度增加约80-90%。在存在普萘洛尔的情况下，白屈菜红碱可阻止去甲肾上腺素引起的I(Cl(swell))增加；在存在哌唑嗪的情况下，KT5720可阻断去甲肾上腺素的抑制作用。结果表明，在兔门静脉肌细胞中，去甲肾上腺素通过作用于α(1)-肾上腺素能受体增强I(Cl(swell))，并通过刺激β-肾上腺素能受体降低I(Cl(swell))。数据表明，去甲肾上腺素的增强和抑制作用分别由PKC和PKA介导。
