α1B 受体与细胞内钙介导交感神经诱导的大鼠虹膜血管收缩。

Alpha 1B-receptors and intracellular calcium mediate sympathetic nerve induced constriction of rat irideal blood vessels.

作者信息

Gould D J, Hill C E

机构信息

Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Act.

出版信息

J Auton Nerv Syst. 1994 Dec 15;50(2):139-50. doi: 10.1016/0165-1838(94)90004-3.

DOI:10.1016/0165-1838(94)90004-3

PMID:7884154

Abstract

The present study has investigated the receptors involved in the non-cholinergic nerve mediated constriction of the larger blood vessels (30-50 microns) within the rat iris. This response was blocked by the alpha-adrenoceptor antagonist, benextramine (10(5) M). Furthermore, the response was more sensitive to blockade by the alpha 1 antagonist, prazosin (IC50 9 x 10(-10) M), than to blockade by the alpha 2 antagonist, yohimbine (IC50 2 x 10(-7) M), or the adrenergic antagonist, WB4101 (IC50 2 x 10(-8) M), and was abolished by chloroethylclonidine (10(-5) M). These results suggest the involvement of alpha 1B-adrenoceptors. The nerve mediated constriction was not blocked by the voltage-dependent calcium channel blocking drugs, nifedipine (10(-6) M), verapamil (10(-6) M) or diltiazem (10(-6) M), but was completely abolished by the intracellular calcium mobilizer, caffeine (10(-3) M), supporting the hypothesis that alpha 1B-adrenoceptors are activated following nerve stimulation. Dantrolene (10(-4) M), which interferes with calcium release from the sarcoplasmic reticulum, reduced the nerve mediated constriction by 40% as did thapsigargin (2 x 10(-6) M), which inhibits the calcium ATPase responsible for uptake of calcium into intracellular stores. When influx of calcium was blocked by verapamil (10(-6) M), thapsigargin, but not dantrolene, completely abolished the response. Noradrenaline (10(-5) M) produced a vasoconstriction in the presence or absence of external calcium although the latter response was significantly smaller than the former. Vasoconstriction produced by a submaximal concentration of noradrenaline (10(-6) M), was completely prevented by pretreatment with chloroethylclonidine. The data indicate that noradrenaline released from sympathetic nerves causes a constriction of arterioles in the iris by activating alpha 1B-adrenoceptors and releasing calcium from dantrolene sensitive and insensitive intracellular stores, followed by inflow of calcium through verapamil sensitive calcium channels. Applied noradrenaline also activates chloroethylclonidine sensitive receptors on the arteriolar surface.

摘要

本研究调查了大鼠虹膜内较大血管（30 - 50微米）非胆碱能神经介导的收缩所涉及的受体。这种反应被α - 肾上腺素能受体拮抗剂苄胺唑啉（10⁻⁵ M）阻断。此外，该反应对α₁拮抗剂哌唑嗪（IC₅₀ 9×10⁻¹⁰ M）的阻断比对α₂拮抗剂育亨宾（IC₅₀ 2×10⁻⁷ M）或肾上腺素能拮抗剂WB4101（IC₅₀ 2×10⁻⁸ M）的阻断更敏感，并且被氯乙可乐定（10⁻⁵ M）消除。这些结果表明涉及α₁B - 肾上腺素能受体。神经介导的收缩未被电压依赖性钙通道阻滞剂硝苯地平（10⁻⁶ M）、维拉帕米（10⁻⁶ M）或地尔硫卓（10⁻⁶ M）阻断，但被细胞内钙动员剂咖啡因（10⁻³ M）完全消除，这支持了神经刺激后α₁B - 肾上腺素能受体被激活的假说。干扰肌浆网钙释放丹曲林（10⁻⁴ M）使神经介导的收缩减少40%，抑制负责将钙摄取到细胞内储存的钙ATP酶的毒胡萝卜素（2×⁻⁶ M）也有同样效果。当维拉帕米（10⁻⁶ M）阻断钙内流时，毒胡萝卜素而非丹曲林完全消除了该反应。去甲肾上腺素（10⁻⁵ M）在有或无细胞外钙存在时均产生血管收缩，尽管后者反应明显小于前者。次最大浓度去甲肾上腺素（10⁻⁶ M）产生的血管收缩可被氯乙可乐定预处理完全阻止。数据表明，交感神经释放的去甲肾上腺素通过激活α₁B - 肾上腺素能受体并从丹曲林敏感和不敏感的细胞内储存中释放钙，随后钙通过维拉帕米敏感的钙通道流入，从而导致虹膜小动脉收缩。应用的去甲肾上腺素还激活小动脉表面的氯乙可乐定敏感受体。