AMP诱导大鼠和豚鼠离体输精管交感神经传递抑制的作用机制。

The mechanism of action of AMP-induced inhibition of sympathetic neurotransmission in the isolated vas deferens of the rat and guinea-pig.

作者信息

Dalziel H H, Sneddon P

机构信息

Department of Physiology and Pharmacology, University of Strathclyde, Glasgow.

出版信息

Br J Pharmacol. 1988 Jul;94(3):961-7. doi: 10.1111/j.1476-5381.1988.tb11610.x.

DOI:10.1111/j.1476-5381.1988.tb11610.x

PMID:2846112

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854020/

Abstract

The proposal that adenosine 5'-monophosphate (AMP) can be used as a selective antagonist of ATP at P2-purinoceptors on smooth muscle was investigated by examining the electrical and mechanical responses of guinea-pig and rat vasa deferentia to stimulation of sympathetic nerves and to exposure to exogenous agonists. 2. The magnitude of the contractile response of the rat vas deferens to field stimulation of the sympathetic nerves was reduced by addition of AMP. This effect was rapid in onset and readily reversed by washout. 3. The action of AMP on these contractile responses was reversed by the subsequent addition of the specific P1-purinoceptor antagonist 8-phenyltheophylline (8-PT). 8-PT on its own had no significant effect on contractile responses to nerve stimulation. 4. The magnitude of excitatory junction potentials (e.j.ps) in the guinea-pig vas deferens evoked by a train of stimuli at 0.5 Hz was reduced in a dose-dependent manner by introduction of AMP (10(-6)-10(-3)M). The inhibitory effect of 10(-5) M AMP on e.j.p. magnitude was completely and rapidly reversed by introduction of 10(-5)M 8-PT. The effect of 10(-4)M AMP was partially reversed by 10(-5) 8-PT. 5. The contractile responses of the guinea-pig vas deferens to exogenously applied adenosine 5'-triphosphate (ATP) were not reduced by AMP, even at a concentration of 2.5 X 10(-4)M. Similarly in the rat vas deferens, contractile responses to exogenously applied alpha, beta-methylene ATP (a more potent P2-purinoceptor agonist) were reduced by only 27.2%. The same concentration of AMP did not affect the contractile responses of the rat vas deferens to noradrenaline. 6. We conclude that the primary mechanism of action of AMP is to inhibit sympathetic neurotransmission by an agonist action at P1-purinoceptors on the sympathetic nerve terminal reducing the release of neurotransmitter, and therefore AMP cannot be used as a selective P2-purinoceptor antagonist.

摘要

通过检测豚鼠和大鼠输精管对交感神经刺激及外源性激动剂的电反应和机械反应，研究了5'-单磷酸腺苷（AMP）可作为平滑肌P2嘌呤受体上ATP选择性拮抗剂的这一假说。2. 添加AMP可降低大鼠输精管对交感神经场刺激的收缩反应幅度。此效应起效迅速，冲洗后易于逆转。3. 随后添加特异性P1嘌呤受体拮抗剂8-苯基茶碱（8-PT）可逆转AMP对这些收缩反应的作用。单独使用8-PT对神经刺激的收缩反应无显著影响。4. 在豚鼠输精管中，以0.5 Hz的一串刺激诱发的兴奋性接头电位（e.j.ps）幅度，会因引入AMP（10⁻⁶ - 10⁻³ M）而呈剂量依赖性降低。10⁻⁵ M AMP对e.j.p.幅度的抑制作用，通过引入10⁻⁵ M 8-PT可完全且迅速逆转。10⁻⁴ M AMP的作用可被10⁻⁵ 8-PT部分逆转。5. 即使在浓度为2.5×10⁻⁴ M时，AMP也不会降低豚鼠输精管对外源性施加的5'-三磷酸腺苷（ATP）的收缩反应。同样，在大鼠输精管中，对外源性施加的α,β-亚甲基ATP（一种更强效的P2嘌呤受体激动剂）的收缩反应仅降低27.2%。相同浓度的AMP不影响大鼠输精管对去甲肾上腺素的收缩反应。6. 我们得出结论，AMP的主要作用机制是通过对交感神经末梢上的P1嘌呤受体的激动作用来抑制交感神经传递，从而减少神经递质的释放，因此AMP不能用作选择性P2嘌呤受体拮抗剂。