Thompson D C, Diamond L, Altiere R J
School of Pharmacy, University of Colorado, Boulder.
J Pharmacol Exp Ther. 1990 Jul;254(1):306-11.
Cholinergic and nonadrenergic noncholinergic (NANC) excitatory nerves in guinea pig trachea are subject to presynaptic alpha-2 adrenoceptor inhibitory control. Although the trachea is also innervated by NANC inhibitory nerves, little is known about their presynaptic regulation. The present study assessed the capacity of alpha-1 and alpha-2 adrenoceptor agonists to modulate NANC inhibitory nerves and for comparison, cholinergic excitatory nerves in guinea pig trachea. To eliminate effects of intrinsic sympathetic nerve stimulation and prostanoid production, tissues were pretreated with guanethidine, propranolol and indomethacin. The alpha-2 adrenoceptor agonist, clonidine (1 microM), induced a 12-fold rightward shift of the frequency-response curve for neurally mediated cholinergic contractions but had no effect on the concentration-response curve for exogenously administered acetylcholine. This action of clonidine was inhibited in a concentration-dependent manner by the alpha-2 adrenoceptor antagonist, yohimbine, and by the alpha-1 adrenoceptor antagonist, prazosin, NANC inhibitory responses were unaffected by clonidine (1 microM). The alpha-1 adrenoceptor agonist, phenylephrine (1 microM), failed to influence responses induced by cholinergic or NANC inhibitory nerve stimulation, acetylcholine or vasoactive intestinal peptide. Furthermore, in tissues treated with propranolol but not subjected to adrenergic neuronal blockade with guanethidine, neurally mediated cholinergic responses were not altered by yohimbine (0.3 microM) treatment. These results indicate that in guinea pig trachea: 1) cholinergic nerves are modulated by presynaptic, prazosin-sensitive inhibitory presynaptic alpha-2 adrenoceptors and 2) NANC inhibitory nerves do not possess presynaptic, modulatory alpha adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
豚鼠气管中的胆碱能和非肾上腺素能非胆碱能（NANC）兴奋性神经受突触前α-2肾上腺素能受体抑制性控制。尽管气管也受NANC抑制性神经支配，但其突触前调节情况却知之甚少。本研究评估了α-1和α-2肾上腺素能受体激动剂对豚鼠气管中NANC抑制性神经以及作为对照的胆碱能兴奋性神经的调节能力。为消除内在交感神经刺激和前列腺素产生的影响，组织先用胍乙啶、普萘洛尔和吲哚美辛进行预处理。α-2肾上腺素能受体激动剂可乐定（1微摩尔）使神经介导的胆碱能收缩的频率-反应曲线向右移动了12倍，但对外源性给予乙酰胆碱的浓度-反应曲线没有影响。可乐定的这一作用被α-2肾上腺素能受体拮抗剂育亨宾以及α-1肾上腺素能受体拮抗剂哌唑嗪以浓度依赖性方式抑制。NANC抑制性反应不受可乐定（1微摩尔）影响。α-1肾上腺素能受体激动剂去氧肾上腺素（1微摩尔）未能影响胆碱能或NANC抑制性神经刺激、乙酰胆碱或血管活性肠肽所诱导的反应。此外，在用普萘洛尔处理但未用胍乙啶进行肾上腺素能神经元阻滞的组织中，育亨宾（0.3微摩尔）处理不会改变神经介导的胆碱能反应。这些结果表明，在豚鼠气管中：1）胆碱能神经受突触前、对哌唑嗪敏感的抑制性突触前α-2肾上腺素能受体调节；2）NANC抑制性神经不具有突触前调节性α-肾上腺素能受体。（摘要截短于250字）
