Boksa P, Livett B G
Brain Res. 1985 Apr 15;332(1):29-38. doi: 10.1016/0006-8993(85)90386-5.
Substance P (SP) has two distinct actions on catecholamine (CA) release from cultured bovine adrenal chromaffin cells: SP inhibits acetylcholine (ACh)- or nicotine-induced [3H]norepinephrine ([3H]NE) release; and SP protects against desensitization of ACh- or nicotine-induced [3H]NE release. In order to characterize the SP receptor subtypes modulating these two actions, we have tested several SP-related tachykinins and SP analogues for their ability to act as agonists of SP for these actions. The naturally occurring tachykinins, physalaemin, eledoisin and kassinin, were about equipotent and all much less potent than SP in inhibiting nicotine-induced [3H]NE release. Physalaemin and eledoisin were also approximately equipotent and much less potent than SP in protecting against desensitization of nicotine-induced [3H]NE release; kassinin slightly enhanced nicotinic desensitization. These results indicate that neither a kassinin-like nor a physalaemin-like peptide are likely to modulate adrenal CA release. The 'SP-P' receptor-selective analogue, SP-methyl ester, was an agonist, equipotent with SP, for both of SP's actions on [3H]NE release. [D-Pro2,D-Trp7,9]-SP, a potent antagonist of SP's actions in many SP-responsive tissues, was inactive as an antagonist of both of SP's actions on [3H]NE release from adrenal chromaffin cells; however, this analogue was a potent SP agonist in chromaffin cells. The rank order of potency of these and other SP-related peptides for inhibition of [3H]NE release was similar to their order of potency for protection against desensitization. Thus the chromaffin cell SP receptors mediating inhibition of nicotine-induced [3H]NE release appear to be very similar to those mediating protection against desensitization of nicotine-induced [3H]NE release. The results indicate that the SP receptors modulating adrenal CA release are different from either the 'SP-P' or 'SP-E' receptor subtypes; bovine adrenal chromaffin cells appear to possess a third subtype of SP receptor which shares similar characteristics with the SP receptors mediating histamine release from rat mast cells.
P物质（SP）对培养的牛肾上腺嗜铬细胞释放儿茶酚胺（CA）有两种不同作用：SP抑制乙酰胆碱（ACh）或尼古丁诱导的[3H]去甲肾上腺素（[3H]NE）释放；并且SP可防止ACh或尼古丁诱导的[3H]NE释放脱敏。为了表征调节这两种作用的SP受体亚型，我们测试了几种与SP相关的速激肽和SP类似物作为SP激动剂发挥这些作用的能力。天然存在的速激肽，蛙皮素、eledoisin和雨蛙肽，在抑制尼古丁诱导的[3H]NE释放方面效力相当且均远低于SP。蛙皮素和eledoisin在防止尼古丁诱导的[3H]NE释放脱敏方面也效力相当且远低于SP；雨蛙肽略微增强了烟碱脱敏作用。这些结果表明，类雨蛙肽样或类蛙皮素样肽均不太可能调节肾上腺CA释放。“SP-P”受体选择性类似物SP甲酯是一种激动剂，在对[3H]NE释放的两种SP作用方面与SP效力相当。[D-脯氨酸2，D-色氨酸7,9]-SP，在许多SP反应性组织中是SP作用的强效拮抗剂，但对肾上腺嗜铬细胞[3H]NE释放的两种SP作用均无拮抗活性；然而，该类似物在嗜铬细胞中是强效的SP激动剂。这些以及其他与SP相关肽抑制[3H]NE释放的效力排序与其防止脱敏的效力排序相似。因此，介导抑制尼古丁诱导的[3H]NE释放的嗜铬细胞SP受体似乎与介导防止尼古丁诱导的[3H]NE释放脱敏的受体非常相似。结果表明，调节肾上腺CA释放的SP受体不同于“SP-P”或“SP-E”受体亚型；牛肾上腺嗜铬细胞似乎拥有第三种SP受体亚型，其与介导大鼠肥大细胞释放组胺的SP受体具有相似特征。
