Doggrell S A
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
J Pharmacol Methods. 1990 Sep;24(2):145-56. doi: 10.1016/0160-5402(90)90025-g.
The rat portal vein has spontaneous mechanical activity. The effects of beta-adrenoceptor agonists and antagonists and verapamil alone and together on this mechanical activity have been determined. Isoprenaline, but not dobutamine, attenuated the contractile activity. Three successive challenges to isoprenaline produced identical attenuation curves. The responses to isoprenaline were antagonized by propranolol, metoprolol, and ICI 118,551, and the pA2 values, derived by Schild analysis, were 9.12, 6.78, and 9.33, respectively. Thus, the rat portal vein contains predominantly beta 2-adrenoceptors. Verapamil attenuated the contractile activity of the rat portal vein, and this attenuation was not altered by the presence of propranolol at 10(-5) M. The potencies of isoprenaline and propranolol were not altered by the presence of a 30% attenuation of the contractile activity with verapamil at 10(-7) M. Thus, the rat portal vein may be used to determine the potencies of drugs as beta 2-adrenoceptor antagonists and as voltage dependent calcium channel blockers. In addition, the potency of drugs as beta 2-adrenoceptor antagonists on the rat portal vein may be determined in the presence of some voltage dependent calcium channel blockade.
大鼠门静脉具有自发的机械活动。已确定β-肾上腺素能受体激动剂、拮抗剂以及维拉帕米单独和联合使用对这种机械活动的影响。异丙肾上腺素可减弱收缩活动，但多巴酚丁胺无此作用。对异丙肾上腺素进行三次连续刺激产生相同的衰减曲线。普萘洛尔、美托洛尔和ICI 118,551可拮抗对异丙肾上腺素的反应，通过Schild分析得出的pA2值分别为9.12、6.78和9.33。因此，大鼠门静脉主要含有β2-肾上腺素能受体。维拉帕米可减弱大鼠门静脉的收缩活动，且在10^(-5)M普萘洛尔存在时这种减弱作用未改变。在10^(-7)M维拉帕米使收缩活动减弱30%的情况下，异丙肾上腺素和普萘洛尔的效价未改变。因此，大鼠门静脉可用于确定作为β2-肾上腺素能受体拮抗剂和电压依赖性钙通道阻滞剂的药物效价。此外，在存在一定程度电压依赖性钙通道阻滞的情况下，可确定药物作为大鼠门静脉β2-肾上腺素能受体拮抗剂的效价。
