Leeuwin R S, Zeegers A, Van Wilgenburg H
Department of Pharmacology, University of Amsterdam, Netherlands.
Eur J Pharmacol. 1996 Mar 28;299(1-3):149-52. doi: 10.1016/0014-2999(95)00866-7.
The influence of the ligand PK 11195 (1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinolinecarboxamide), antagonist of the peripheral-type benzodiazepine receptor, on the inotropic response of the perfused rat heart to diazepam (7-chloro-5-phenyl-methyl- 1,3-dihydro-2H-1,4-benzodiazepin-2-one) was studied. Diazepam induced a positive inotropic response which was preceded by a transient negative inotropic response. Concentrations of 10(-7) M PK 11195 were ineffective, whereas concentrations of 10(-6) and 10(-5) M PK 11195 reduced the positive inotropic response significantly. At 5 x 10(-5) M PK 11195 the response was completely abolished. The negative inotropic response was not changed by either concentration of PK 11195 used. It is concluded that the positive inotropic response of the isolated rat heart to diazepam may well be mediated through peripheral-type benzodiazepine receptors; the negative inotropic response must be related to other (more complex) mechanisms.
研究了外周型苯二氮䓬受体拮抗剂配体PK 11195（1-(2-氯苯基)-N-甲基-N-(1-甲基丙基)-3-异喹啉甲酰胺）对灌注大鼠心脏对地西泮（7-氯-5-苯基甲基-1,3-二氢-2H-1,4-苯并二氮杂䓬-2-酮）的变力性反应的影响。地西泮诱导出正性变力性反应，在此之前有一个短暂的负性变力性反应。10(-7) M的PK 11195浓度无效，而10(-6) M和10(-5) M的PK 11195浓度则显著降低了正性变力性反应。在5×10(-5) M的PK 11195浓度下，反应完全被消除。所用的任何一种PK 11195浓度都没有改变负性变力性反应。得出的结论是，离体大鼠心脏对地西泮的正性变力性反应很可能是通过外周型苯二氮䓬受体介导的；负性变力性反应一定与其他（更复杂的）机制有关。
