P物质调节大鼠灌流肾上腺中烟碱样而非毒蕈碱样儿茶酚胺分泌的时间进程。

Substance P modulates the time course of nicotinic but not muscarinic catecholamine secretion from perfused adrenal glands of rat.

作者信息

Zhou X F, Marley P D, Livett B G

机构信息

Department of Biochemistry, University of Melbourne, Parkville, Vic., Australia.

出版信息

Br J Pharmacol. 1991 Sep;104(1):159-65. doi: 10.1111/j.1476-5381.1991.tb12401.x.

DOI:10.1111/j.1476-5381.1991.tb12401.x

PMID:1723914

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1908299/

Abstract

Substance P (SP) and acetylcholine (ACh) are contained within the splanchnic nerve terminals in the adrenal gland and can be released in response to stress. In the rat, the release of aCh brings about secretion of catecholamines (CA) by acting on nicotinic and muscarinic receptors on the adrenal chromaffin cells. 2. In the present study, we have used a rat isolated adrenal gland preparation to investigate the effects of SP, perfused at different concentrations, on CA secretion evoked by 10(-5) M nicotine and 10(-4) M muscarine. 3. In the first 10 min stimulation period (S1), in the absence of SP, nicotine (10(-5) M) evoked substantial and equal secretion of noradrenaline (NA) and adrenaline (Ad). In a second 10 min stimulation period (S2), carried out 18 min after S1, the nicotinic response was desensitized. In contrast, the muscarinic response, which preferentially evoked Ad secretion in S1 (Ad/NA: 8.7/1), was well maintained in S2. 4. SP present in S1 had no effect on desensitization of the subsequent nicotinic response in S2. 5. At low concentrations (10(-7)-10(-10) M), SP changed the time course of nicotine-induced CA secretion during S1 by enhancing CA secretion in the first 4 min and inhibiting CA secretion thereafter. The maximal effect occurred at 10(-9) M SP. 6. At a higher concentration (10(-5) M), SP inhibited total nicotinic CA secretion throughout S1 and produced a biphasic secretion of CA (depressed in the presence of SP and enhanced after wash out of SP). Pre-exposure of adrenal glands to SP (10-' to 10- M) for 10min produced marked inhibition of the nicotine-induced CA secretion. 7. In contrast to the effect of SP on the nicotinic response, SP from 10- to 10-SM had no effect on muscarinic CA secretion. 8. This difference in sensitivity of the nicotinic and muscarinic responses to SP points to a diversity of mechanisms available for control of adrenal catecholamine secretion. In addition to the ability of SP to increase or decrease the total amount of adrenal CA secretion, dependent on the concentration of SP, the present study shows that SP can change the time-course of nicotinic CA secretion. These results with the rat adrenal gland perfused in vitro suggests both a quantitative and temporal role for SP as a novel modulator of adrenal CA secretion.

摘要

P物质（SP）和乙酰胆碱（ACh）存在于肾上腺的内脏神经末梢内，可在应激反应时释放。在大鼠中，ACh的释放通过作用于肾上腺嗜铬细胞上的烟碱样和毒蕈碱样受体，引起儿茶酚胺（CA）分泌。2. 在本研究中，我们使用大鼠离体肾上腺制备物，研究不同浓度灌注的SP对由10⁻⁵M尼古丁和10⁻⁴M毒蕈碱诱发的CA分泌的影响。3. 在最初10分钟的刺激期（S1），在不存在SP的情况下，尼古丁（10⁻⁵M）引起去甲肾上腺素（NA）和肾上腺素（Ad）大量且等量的分泌。在S1后18分钟进行的第二个10分钟刺激期（S2）中，烟碱样反应脱敏。相比之下，在S1中优先诱发Ad分泌的毒蕈碱样反应（Ad/NA：8.7/1）在S2中得到良好维持。4. S1中存在的SP对S2中随后的烟碱样反应脱敏没有影响。5. 在低浓度（10⁻⁷ - 10⁻¹⁰M）时，SP通过在最初4分钟增强CA分泌并在其后抑制CA分泌，改变了S1期间尼古丁诱导的CA分泌的时间进程。最大效应出现在10⁻⁹M的SP时。6. 在较高浓度（10⁻⁵M）时，SP在整个S1期间抑制总的烟碱样CA分泌，并产生CA的双相分泌（在存在SP时受到抑制，在洗去SP后增强）。将肾上腺预先暴露于SP（10⁻⁶至10⁻⁵M）10分钟，可显著抑制尼古丁诱导的CA分泌。7. 与SP对烟碱样反应的作用相反，10⁻⁶至10⁻⁵M的SP对毒蕈碱样CA分泌没有影响。8. 烟碱样和毒蕈碱样反应对SP敏感性的这种差异表明，存在多种可用于控制肾上腺儿茶酚胺分泌的机制。除了SP根据其浓度增加或减少肾上腺CA分泌总量的能力外，本研究表明SP可以改变烟碱样CA分泌的时间进程。这些对体外灌注大鼠肾上腺的研究结果表明，SP作为肾上腺CA分泌的新型调节剂，在数量和时间上均发挥作用。