Endoh M, Takanashi M, Norota I
Department of Pharmacology, Yamagata University School of Medicine, Japan.
Eur J Pharmacol. 1992 Nov 17;223(2-3):143-51. doi: 10.1016/0014-2999(92)94832-g.
The influence of the alpha 1A-adrenoceptor subtype-selective antagonist (+)-niguldipine on the alpha 1-mediated positive inotropic effect was assessed in the isolated rabbit ventricular myocardium. (+)-Niguldipine displaced the specific binding of [3H]prazosin to a membrane fraction derived from rabbit ventricular muscle with high (Ki = 64.6 pmol/l; RH = 23%) and low (Ki = 7.08 nmol/l) affinity. (+)-Niguldipine displaced specific [3H]CGP-121177 binding only at very high concentrations (Ki = 118 nmol/l). (+)-Niguldipine at 0.1 pmol/l and higher shifted the concentration-response curve for the alpha 1-mediated positive inotropic effect downwards, but at higher concentrations (up to 10 and 100 nmol/l) it did not cause a further shift of the curve. (+)-Niguldipine (1-100 nmol/l) did not affect the beta-mediated positive inotropic effect and the basal force of concentration. (-)-Niguldipine also showed a selective inhibitory action on the alpha 1-adrenoceptor-mediated positive inotropic effect, but its affinity and potency were approximately 1-2 log units lower than those of (+)-niguldipine. The present results indicate that the alpha 1A-adrenoceptor subtype is involved in the alpha 1-mediated positive inotropic effect. (+)-Niguldipine (or (-)-niguldipine with lower affinity) is able to antagonize selectively the cardiac alpha 1A-adrenoceptor-mediated positive inotropic effect. The magnitude of the alpha 1A-mediated inotropic effect, however, may be much less than that mediated by the alpha 1B-subtype in the rabbit ventricular myocardium.
在离体兔心室肌中评估了α1A -肾上腺素能受体亚型选择性拮抗剂（+）-尼群地平对α1介导的正性肌力作用的影响。（+）-尼群地平以高亲和力（Ki = 64.6 pmol/l；相对亲和力（RH）= 23%）和低亲和力（Ki = 7.08 nmol/l）取代[3H]哌唑嗪与兔心室肌膜组分的特异性结合。（+）-尼群地平仅在非常高的浓度下（Ki = 118 nmol/l）才能取代特异性[3H]CGP - 121177结合。0.1 pmol/l及更高浓度的（+）-尼群地平使α1介导的正性肌力作用的浓度 - 反应曲线向下移动，但在更高浓度（高达10和100 nmol/l）时，它并未使曲线进一步移动。（+）-尼群地平（1 - 100 nmol/l）不影响β介导的正性肌力作用和基础收缩力。（-）-尼群地平对α1 -肾上腺素能受体介导的正性肌力作用也表现出选择性抑制作用，但其亲和力和效能比（+）-尼群地平低约1 - 2个对数单位。目前的结果表明，α1A -肾上腺素能受体亚型参与了α1介导的正性肌力作用。（+）-尼群地平（或亲和力较低的（-）-尼群地平）能够选择性拮抗心脏α1A -肾上腺素能受体介导地正性肌力作用。然而，在兔心室肌中，α1A介导的正性肌力作用的幅度可能远小于α1B亚型介导的幅度。
