Mantelli L, Capanni L, Corti V, Bennardini F, Matucci R, Ledda F
Department of Pharmacology, University of Florence, Italy.
Eur J Pharmacol. 1988 May 20;150(1-2):123-9. doi: 10.1016/0014-2999(88)90757-1.
The influence of lithium on the positive inotropic effects mediated by alpha- and beta-adrenoceptor stimulation was studied in isolated guinea-pig ventricular preparations stimulated at 1 Hz. Lithium chloride (10(-3)-2 X 10(-2) M) shifted the concentration-response curve for the inotropic effect of phenylephrine to the right in a dose-dependent manner. [3H]Prazosin binding was not inhibited by 10(-2) M lithium. The antagonistic effect of lithium was almost completely prevented by the presence of 10(-2) M myoinositol, and was potentiated by 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol, an antagonist of myo-inositol. The positive inotropic effect of isoprenaline was completely unaffected by either 10(-2) M lithium, 10(-2) M myo-inositol, or 10(-4) M 2-2'-anhydro-2-C-(hydroxymethyl)-myo-inositol. Since it is known that lithium interferes with inositol phosphate metabolism, our results produce further indirect evidence of an involvement of inositol phosphates in the myocardial response to alpha-adrenoceptor, but not to beta-adrenoceptor, stimulation. Our findings also suggest that chronic lithium treatment could interfere with the adrenergic modulation of myocardial contractility in those physio-pathological conditions in which the role of myocardial alpha-adrenoceptors becomes predominant.
在以1Hz频率刺激的豚鼠离体心室标本中，研究了锂对由α和β肾上腺素能受体刺激介导的正性肌力作用的影响。氯化锂（10⁻³ - 2×10⁻²M）使去氧肾上腺素正性肌力作用的浓度 - 反应曲线以剂量依赖方式右移。10⁻²M锂不抑制[³H]哌唑嗪结合。10⁻²M肌醇的存在几乎完全阻止了锂的拮抗作用，而10⁻⁴M 2 - 2'-脱水 - 2 - C -（羟甲基）- 肌醇（一种肌醇拮抗剂）增强了该作用。异丙肾上腺素的正性肌力作用完全不受10⁻²M锂、10⁻²M肌醇或10⁻⁴M 2 - 2'-脱水 - 2 - C -（羟甲基）- 肌醇的影响。由于已知锂会干扰肌醇磷酸代谢，我们的结果进一步间接证明了肌醇磷酸参与心肌对α肾上腺素能受体而非β肾上腺素能受体刺激的反应。我们的发现还表明，在心肌α肾上腺素能受体作用占主导的生理病理条件下，长期锂治疗可能会干扰心肌收缩力的肾上腺素能调节。
