Starke K, von Kügelgen I, Driessen B, Bültmann R
Pharmakologisches Institut, Albert Ludwigs-Universität Freiburg, Freiburg im Breisgau, Germany.
Ciba Found Symp. 1996;198:239-49; discussion 249-59. doi: 10.1002/9780470514900.ch14.
We studied some properties of the release of noradrenaline and ATP in isolated sympathetically innervated tissues. Release was elicited by electric stimulation and assessed as overflow of tritiated compounds (after labelling with [3H]noradrenaline) and enzymically measured ATP, respectively. Evans blue, which inhibits ectonucleotidases, greatly increased the evoked overflow of ATP, indicating that a major part of the ATP was metabolized after release. Much of the ATP was postjunctional in origin. The neural fraction was isolated when postjunctional release was suppressed by prazosin (alpha 1-adrenoceptor antagonist) and suramin (P2 purinoceptor antagonist). Comparison of neural ATP and [3H]-noradrenaline release showed that prostaglandin E2 reduced the release of both co-transmitters to a similar extent. Activation of prejunctional alpha 2-adrenoceptors, however, preferentially reduced the release of [3H]noradrenaline, and activation of prejunctional A1 purinoceptors reduced preferentially the release of ATP. Nucleotides such as ATP depressed the release of [3H]noradrenaline through two receptors: the well-known prejunctional A1 receptors and a separate group of prejunctional P2 purinoceptors. P2 antagonists increased the release of [3H]-noradrenaline. Overall, the results indicate differential storage, release and modulation of release of the two sympathetic co-transmitters. They also indicate that postganglionic sympathetic axons possess receptors for both co-transmitters: alpha 2 and P2 autoreceptors.
我们研究了去甲肾上腺素和三磷酸腺苷(ATP)在离体交感神经支配组织中的释放特性。通过电刺激引发释放,并分别将其评估为氚标记化合物(用[3H]去甲肾上腺素标记后)的溢出量和酶法测定的ATP量。抑制外核苷酸酶的伊文思蓝极大地增加了诱发的ATP溢出量,这表明大部分ATP在释放后被代谢。大部分ATP起源于节后。当通过哌唑嗪(α1肾上腺素能受体拮抗剂)和苏拉明(P2嘌呤受体拮抗剂)抑制节后释放时,可分离出神经部分。神经ATP释放与[3H] - 去甲肾上腺素释放的比较表明,前列腺素E2以相似程度降低了两种共递质的释放。然而,节前α2肾上腺素能受体的激活优先降低了[3H]去甲肾上腺素的释放,而节前A1嘌呤受体的激活优先降低了ATP的释放。诸如ATP之类的核苷酸通过两种受体抑制[3H]去甲肾上腺素的释放:著名的节前A1受体和另一组节前P2嘌呤受体。P2拮抗剂增加了[3H] - 去甲肾上腺素的释放。总体而言,结果表明两种交感神经共递质在储存、释放及释放调节方面存在差异。它们还表明节后交感神经轴突拥有两种共递质的受体:α2和P2自受体。