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关于血小板活化因子对心肌的作用机制

On the mechanisms of action of PAF on the myocardium.

作者信息

Gollasch M, Ignatieva V B, Kobrinsky E M, Vornovitsky E G

机构信息

Institute of Physiology, Humboldt-University, Berlin, Germany.

出版信息

Bratisl Lek Listy. 1991 Mar-Apr;92(3-4):159-64.

PMID:2029657
Abstract

The effects of PAF (1-2 X 10(-7) M) on intracellular slow Ca-mediated action potentials (Ca-AP) and isometric contractions of guinea-pig auricle muscles and ionic currents of frog atrial trabeculae were investigated. PAF decreased the amplitude, duration and upstroke velocity of the slow Ca-AP mediated via the L-type Ca channels in guinea-pig auricle muscles without changes in the resting potential. The PAF receptor antagonist U-66985 (1-5 X 10(-6) M), histamine (10(-4) M) and 4-aminopyridine (3 mM) inhibited the depressant effects of PAF on the slow AP and contractions. PAF reduced the peak of the slow inward Ca current (ICa) via the L-type Ca channels of frog atrial trabeculae. Simultaneously, the delayed outward K current (IK) was increased by PAF. Pretreatment with the PAF receptor antagonist BN 52021 (4 X 10(-6) M) protected the effects of PAF on ICa and IK. Our data demonstrate both by direct and indirect methods of ICa registration an inhibiting effect of PAF on the ICa via the L-type Ca channels and make probable a similarity in PAF signalling in cardiac cells of cold- and warm-blooded animals. The coupling of changes of the ICa with the augmentation of IK accentuate the important role of myocardial L-type Ca and K channels in mediating the negative inotropic action of PAF. The ability of U-66985 and BN 52021 to inhibit the electrophysiological effects of PAF hint at a membrane signalling coupled by specific binding sites for PAF in the myocardium.

摘要

研究了血小板活化因子(PAF,1 - 2×10⁻⁷ M)对豚鼠耳廓肌细胞内慢钙介导动作电位(Ca - AP)、等长收缩以及青蛙心房小梁离子电流的影响。PAF降低了豚鼠耳廓肌中通过L型钙通道介导的慢Ca - AP的幅度、持续时间和上升速度,而静息电位无变化。PAF受体拮抗剂U - 66985(1 - 5×10⁻⁶ M)、组胺(10⁻⁴ M)和4 - 氨基吡啶(3 mM)可抑制PAF对慢动作电位和收缩的抑制作用。PAF降低了青蛙心房小梁通过L型钙通道的慢内向钙电流(ICa)峰值。同时,PAF使延迟外向钾电流(IK)增加。用PAF受体拮抗剂BN 52021(4×10⁻⁶ M)预处理可保护PAF对ICa和IK的作用。我们的数据通过直接和间接记录ICa的方法都证明了PAF对通过L型钙通道的ICa有抑制作用,并表明冷血和温血动物心脏细胞中PAF信号传导可能存在相似性。ICa变化与IK增加的耦合突出了心肌L型钙通道和钾通道在介导PAF负性肌力作用中的重要作用。U - 66985和BN 52021抑制PAF电生理效应的能力提示心肌中存在与PAF特异性结合位点偶联的膜信号传导。

相似文献

1
On the mechanisms of action of PAF on the myocardium.关于血小板活化因子对心肌的作用机制
Bratisl Lek Listy. 1991 Mar-Apr;92(3-4):159-64.
2
[The blocking action of platelet-activating factor (PAF) on the calcium currents of the atrial fibers in the frog and guinea pig].[血小板活化因子(PAF)对青蛙和豚鼠心房纤维钙电流的阻断作用]
Biull Eksp Biol Med. 1989 Dec;108(12):643-6.
3
Electrophysiological mechanisms responsible for the action of PAF in guinea-pig myocardium. Relation to the putative membrane signalling processes of PAF.血小板活化因子在豚鼠心肌中发挥作用的电生理机制。与血小板活化因子假定的膜信号传导过程的关系。
J Lipid Mediat. 1991 Mar-Apr;3(2):139-59.
4
Cellular electrophysiological effects of platelet-activating factor (PAF) and its antagonist BN 52021 in cardiac preparations.血小板活化因子(PAF)及其拮抗剂BN 52021对心脏制剂的细胞电生理效应。
Drugs Exp Clin Res. 1992;18(1):9-16.
5
The role of platelet-activating factor (PAF) antagonists and nitric oxide in cardiac actions of PAF. Electrophysiological and morphological study.血小板活化因子(PAF)拮抗剂和一氧化氮在PAF心脏作用中的角色。电生理和形态学研究。
J Physiol Pharmacol. 2000 Dec;51(4 Pt 1):723-35.
6
Effects of platelet activating factor on contractile force and 45Ca fluxes in guinea-pig isolated atria.血小板活化因子对豚鼠离体心房收缩力和45Ca通量的影响。
Br J Pharmacol. 1990 Jun;100(2):305-11. doi: 10.1111/j.1476-5381.1990.tb15800.x.
7
[Cardiodepressive effect of platelet activating factor].[血小板活化因子的心脏抑制作用]
Biull Eksp Biol Med. 1989 Jan;107(1):27-30.
8
[Interactions of PAF and its antagonists in the guinea pig atrial myocardium].[血小板活化因子及其拮抗剂在豚鼠心房肌中的相互作用]
Biull Eksp Biol Med. 1989 Aug;108(8):137-9.
9
Effects of platelet activating factor (PAF) and its receptor antagonist BN 52021 on isolated perfused guinea-pig heart.血小板活化因子(PAF)及其受体拮抗剂BN 52021对豚鼠离体灌注心脏的影响。
Prostaglandins Leukot Essent Fatty Acids. 1989 Dec;38(3):189-94. doi: 10.1016/0952-3278(89)90071-9.
10
Negative inotropic effect of platelet-activating factor: association with a decrease in intracellular sodium activity.血小板活化因子的负性肌力作用:与细胞内钠活性降低相关
J Pharmacol Exp Ther. 1988 Apr;245(1):124-8.