咖啡因与普鲁卡因对豚鼠肠系膜动脉去甲肾上腺素能传递影响的比较。

Comparison of the effects of caffeine and procaine on noradrenergic transmission in the guinea-pig mesenteric artery.

作者信息

Fujii K, Miyahara H, Suzuki H

出版信息

Br J Pharmacol. 1985 Mar;84(3):675-84. doi: 10.1111/j.1476-5381.1985.tb16149.x.

DOI:10.1111/j.1476-5381.1985.tb16149.x

PMID:2985160

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1987137/

Abstract

The effects of caffeine and procaine on noradrenergic transmission in the guinea-pig mesenteric artery were investigated by recording electrical responses of smooth muscle cells and by measuring the outflow of noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DOPEG) induced by perivascular nerve stimulation. Caffeine possessed dual actions on the membrane, i.e., at low concentrations (2.5 X 10(-4)-5 X 10(-4)M), it hyperpolarized the membrane and decreased the membrane resistance and at high concentrations (over 2.5 X 10(-3)M) it depolarized the membrane and increased the membrane resistance. Procaine (over 10(-4)M) consistently depolarized the membrane and increased the membrane resistance. The amplitude of the excitatory junction potential (e.j.p.) produced by perivascular nerve stimulation was increased by low concentrations of procaine (2.5 X 10(-5)-10(-4)M) or high concentrations (10(-3)-5 X 10(-3)M) of caffeine and was decreased by low concentrations of caffeine (2.5 X 10(-5)-10(-4)M) or high concentrations of procaine (5 X 10(-4)-10(-3)M). Higher concentrations of caffeine (over 5 X 10(-3)M) induced a spike potential on the e.j.p., while higher concentrations of procaine (over 2.5 X 10(-3)M) inhibited the generation of e.j.ps. Facilitation of e.j.ps produced by repetitive stimulation of perivascular nerves remained unchanged by caffeine, while it was enhanced by procaine at any given concentration (caffeine 2.5 X 10(-4)-10(-3)M; procaine 10(-4)-10(-3)M). The membrane depolarization produced by exogenously applied NA (10(-5)M) was not blocked by pretreatment with procaine. Conduction velocity of perivascular nerve excitation remained unchanged by application of caffeine (up to 5 X 10(-3)M), and was reduced by application of procaine (over 2.5 X 10(-4)M). Outflow of NA during perivascular nerve stimulation remained unchanged by caffeine (10(-4)-3 X 10(-3)M), while it was enhanced by procaine (over 2.5 X 10(-4)M). The outflow of DOPEG was slightly reduced by caffeine (10(-3)-5 X 10(-3)M) and by lower concentrations of procaine (10(-4)-2.5 X 10(-4)M) but was not altered by higher concentrations of procaine (10(-3)-5 X 10(-3)M). It is concluded that in the guinea-pig mesenteric artery, high concentrations of caffeine (over 10(-3)M) increased the e.j.p. amplitude which might be due to an increase in membrane resistance of the smooth muscle cells. No marked effect of caffeine was observed on transmitter release from the nerve terminals. Procaine (over 2.5 X 10(-4)M) increased transmitter release from perivascular nerves and blocked the re-uptake mechanism of released NA. The mechanisms underlying the decrease in ej.p. amplitude by procaine remain to be determined.

摘要

通过记录平滑肌细胞的电反应以及测量血管周围神经刺激诱导的去甲肾上腺素（NA）和3,4 - 二羟基苯乙二醇（DOPEG）的流出量，研究了咖啡因和普鲁卡因对豚鼠肠系膜动脉去甲肾上腺素能传递的影响。咖啡因对细胞膜具有双重作用，即低浓度（2.5×10⁻⁴ - 5×10⁻⁴M）时，它使细胞膜超极化并降低膜电阻；高浓度（超过2.5×10⁻³M）时，它使细胞膜去极化并增加膜电阻。普鲁卡因（超过10⁻⁴M）持续使细胞膜去极化并增加膜电阻。血管周围神经刺激产生的兴奋性接头电位（e.j.p.）的幅度在低浓度普鲁卡因（2.5×10⁻⁵ - 10⁻⁴M）或高浓度咖啡因（10⁻³ - 5×10⁻³M）作用下增加，而在低浓度咖啡因（2.5×10⁻⁵ - 10⁻⁴M）或高浓度普鲁卡因（5×10⁻⁴ - 10⁻³M）作用下降低。更高浓度的咖啡因（超过5×10⁻³M）在e.j.p.上诱导出一个锋电位，而更高浓度的普鲁卡因（超过2.5×10⁻³M）抑制e.j.ps的产生。重复刺激血管周围神经产生的e.j.ps的易化作用在咖啡因作用下保持不变，而在任何给定浓度（咖啡因2.5×10⁻⁴ - 10⁻³M；普鲁卡因10⁻⁴ - 10⁻³M）的普鲁卡因作用下增强。外源性应用NA（10⁻⁵M）产生的细胞膜去极化不受普鲁卡因预处理的阻断。应用咖啡因（高达5×10⁻³M）时，血管周围神经兴奋的传导速度保持不变，而应用普鲁卡因（超过2.5×10⁻⁴M）时传导速度降低。血管周围神经刺激期间NA的流出量在咖啡因（10⁻⁴ - 3×10⁻³M）作用下保持不变，而在普鲁卡因（超过2.5×10⁻⁴M）作用下增加。DOPEG的流出量在咖啡因（10⁻³ - 5×10⁻³M）和较低浓度的普鲁卡因（10⁻⁴ - 2.5×10⁻⁴M）作用下略有减少，但在较高浓度的普鲁卡因（10⁻³ - 5×10⁻³M）作用下未改变。结论是，在豚鼠肠系膜动脉中，高浓度咖啡因（超过10⁻³M）增加了e.j.p.幅度，这可能是由于平滑肌细胞膜电阻增加所致。未观察到咖啡因对神经末梢递质释放有明显影响。普鲁卡因（超过2.5×10⁻⁴M）增加了血管周围神经递质的释放并阻断了释放的NA的再摄取机制。普鲁卡因导致e.j.p.幅度降低的潜在机制有待确定。