Peptide modulation of ACh receptor desensitization controls neurotransmitter release from chicken sympathetic neurons.
Peptide modulation of ACh receptor desensitization controls neurotransmitter release from chicken sympathetic neurons.
复制标题
ACh 受体脱敏的肽调节控制鸡交感神经元的神经递质释放。
DOI：
10.1152/jn.1993.69.3.928
复制
发表时间：
1993
影响因子：
2.5
通讯作者：
Role,LW
中科院分区：
文献类型：
--
作者：
Valenta,DC;Downing,JE;Role,LW
1.应用免疫组织化学和放射免疫法分别对鸡胚腰交感神经节内P物质(SP)的分布和释放进行了研究。在单个交感神经元周围的神经纤维中可检测到SP免疫反应，并可通过神经节去极化释放。2.采用全细胞膜片钳技术观察SP对体外培养的胚胎交感神经元烟碱型乙酰胆碱受体(AChR)功能的影响。SP(0.1-20微米)可加速ACh诱发电流的衰减(脱敏)速度。乙酰胆碱受体脱敏的时间过程是双相的，可用两个依赖于激动剂浓度的指数函数之和来描述(快成分的时间常数tau f=1-2 S，慢成分的时间常数tau S=10-25 S)。SP选择性地降低了T_u、S和慢分量对电流总衰减率的贡献。SP的脱敏作用具有浓度依赖性和可逆性。SP使脱敏恢复速度减慢2.5倍。3.SP使ACh脱敏的剂量-反应曲线移动，使产生半最大脱敏所需的ACh浓度减少近两倍。4.预先应用SP相当于SP与ACh合用加速AChR脱敏。SP不改变ACh、氨基甲酰胆碱(CARB)或二甲基苯基哌嗪(DMPP)非脱敏浓度所诱发电流的时程。这些数据表明，AChR的激活既不是多肽调节受体功能的必要条件，也不是充分条件。本文提出了SP对乙酰胆碱受体脱敏特定步骤的影响的动力学模型。5.SP可提高体外支配交感神经元突触电流的衰减率，使突触电流时程缩短达80%。6.通过测定去甲肾上腺素(NE)的释放量来评价SP对交感神经元神经递质释放的影响。ACh和CARB以浓度和钙依赖的方式刺激NE的释放。SP单独对去甲肾上腺素(NE)分泌无影响，但对ACh或CARB诱导的去甲肾上腺素(NE)释放有40-50%的抑制作用。7.尽管烟碱受体或毒扁豆碱受体的激动剂都能刺激去甲肾上腺素的释放，但SP选择性地抑制递质分泌中的烟碱成分。因此，SP可抑制DMPP诱导的NE释放高达80%，但对毒鼠强或去极化诱导的NE分泌无影响。8.对SP对全细胞电流和NE分泌的调制作用的平行研究表明，SP对交感神经元递质释放的抑制作用与AChR脱敏的增强程度成正比。
1. The distribution and release of substance P (SP) in embryonic chicken lumbar sympathetic ganglia was examined with the use of immunohistochemistry and radioimmunoassay, respectively. SP immunoreactivity was detected in nerve fibers surrounding individual sympathetic neurons and was released by ganglionic depolarization. 2. Effects of SP on nicotinic acetylcholine receptor (AChR) function was assayed in embryonic sympathetic neurons in vitro by whole-cell patch clamp. SP (0.1–20 microM) accelerated the rate of decay (desensitization) of ACh-induced currents. The AChR desensitization time course is biphasic and described by the sum of two exponential functions dependent on agonist concentration (time constant of the faster component, tau f = 1-2 s, and the slower time constant, tau s = 10-25 s). SP selectively decreased tau s and the contribution of the slow component to the overall rate of current decay. The effects of SP on desensitization were concentration dependent and reversible. SP slowed recovery from desensitization by 2.5-fold. 3. SP shifted the dose-response curve for ACh-induced desensitization, reducing the concentration of ACh required to produce half-maximal desensitization by approximately twofold. 4. Preapplication of SP was equivalent to SP applied together with ACh in accelerating AChR desensitization. SP did not alter the time course of currents elicited by nondesensitizing concentrations of ACh, carbamylcholine (CARB), or dimethylphenylpiperazinium (DMPP). These data suggest that AChR activation is neither necessary nor sufficient for the peptide to modulate receptor function. A kinetic model of the effects of SP on specific steps in AChR desensitization is presented. 5. SP enhanced the rate of decay of synaptic currents in sympathetic neurons innervated in vitro, decreasing the synaptic current duration by up to 80%. 6. Effects of SP on neurotransmitter release from sympathetic neurons were evaluated by measuring the release of [3H]-norepinephrine (NE). ACh and CARB stimulated NE release in a concentration- and calcium-dependent manner. SP alone had no effect on NE secretion, but the peptide inhibited NE release induced by ACh or CARB by 40–50%. 7. Although agonists specific for either nicotinic or muscarinic receptors stimulated release of NE, SP selectively inhibited the nicotinic component of transmitter secretion. Thus SP suppressed NE release induced by DMPP by up to 80% but had no effect on muscarine or depolarization-induced NE secretion. 8. Parallel studies of the modulatory effects of SP on whole-cell currents and NE secretion revealed that SP inhibition of transmitter release from sympathetic neurons is directly proportional to the extent of potentiation of AChR desensitization.(ABSTRACT TRUNCATED AT 400 WORDS)