嘌呤化合物对离体豚鼠心房产生的正负影响。

Negative and positive influences exerted by purine compounds on isolated guinea-pig atria.

Dorigo P, Gaion R M, Maragno I

Department of Pharmacology, University of Padova, Italy.

J Auton Pharmacol. 1988 Sep;8(3):191-6. doi: 10.1111/j.1474-8673.1988.tb00182.x.

Abstract

In spontaneously beating atria isolated from reserpine-treated guinea-pig adenosine, AMP, ADP, ATP (2 microM) and alpha, beta-methylene ATP (0.4 microM) induced a dual effect: a short lasting negative response, characterized by a reduction in contractile force and in frequency rate, followed by a positive phase of increased inotropism and chronotropism. N6-phenylisopropyladenosine (5 nM) induced only the depressant effects whereas inosine (2 microM) was completely inactive. 2. The early, negative influences were antagonized by 8-phenyltheophylline (0.5-10 microM), an alkylxanthine that competes with purines for P1 receptors. 3. The late, positive response was potentiated by 8-phenyltheophylline (0.5-10 microM) and suppressed by quinidine (5 microM), that blocks the effects of adenine compounds mediated by P2 receptors. 4. In spontaneously beating as well as in electrically driven atria, desensitization of P2 purinoceptors by long lasting exposure to alpha, beta-methylene ATP (8 microM) abolished the late positive response to ATP. In preparations treated with both alpha, beta-methylene ATP and 8-phenyltheophylline, ATP was ineffective. 5. These results suggest that, besides P1 receptors, P2 receptors are also present in guinea-pig atria, mediating stimulatory effects of adenine compounds.

摘要

在从经利血平处理的豚鼠分离出的自主搏动心房中，腺苷、AMP、ADP、ATP（2微摩尔）和α,β-亚甲基ATP（0.4微摩尔）诱导了双重效应：一种短暂的负性反应，其特征为收缩力和频率降低，随后是正性变力性和变时性增加的阶段。N6-苯异丙基腺苷（5纳摩尔）仅诱导抑制效应，而肌苷（2微摩尔）则完全无活性。2. 早期的负性影响被8-苯基茶碱（0.5 - 10微摩尔）拮抗，8-苯基茶碱是一种与嘌呤竞争P1受体的烷基黄嘌呤。3. 后期的正性反应被8-苯基茶碱（0.5 - 10微摩尔）增强，并被奎尼丁（5微摩尔）抑制，奎尼丁可阻断由P2受体介导的腺嘌呤化合物的效应。4. 在自主搏动以及电驱动的心房中，通过长时间暴露于α,β-亚甲基ATP（8微摩尔）使P2嘌呤受体脱敏，消除了对ATP的后期正性反应。在用α,β-亚甲基ATP和8-苯基茶碱处理的制剂中，ATP无效。5. 这些结果表明，除P1受体外，P2受体也存在于豚鼠心房中，介导腺嘌呤化合物的刺激效应。