Taneja D T, Clarke D E
Institute of Pharmacology, Syntex Research, Palo Alto, California.
J Pharmacol Exp Ther. 1992 Jan;260(1):192-200.
Indirect evidence suggests that beta-1 adrenoceptors in the guinea pig ileum are innervated but it has not been determined whether "atypical" beta adrenoceptors also receive a postganglionic sympathetic innervation. To answer this question, experiments were undertaken using electrical stimulation of para-arterial sympathetic neurons to evoke relaxation in isolated segments of guinea pig ileum. Tension was developed in the ileal segments by either transmural electrical field stimulation to evoke the cholinergic "twitch" response, or by histamine to produce a steady-state contracture. Para-arterial sympathetic nerve stimulation evoked a frequency-dependent inhibition of the twitch response which was blocked by guanethidine and restored by dexamphetamine, indicating typical noradrenergic transmission. In preparations contracted with histamine and pretreated with benextramine to block alpha adrenoceptors, para-arterial sympathetic nerve stimulation evoked frequency-dependent relaxations which were reduced in magnitude but not abolished by the following beta adrenoceptor antagonists: bromoacetylalprenololmenthane (1 microM) or a combination of ICI 118,551 (0.3 microM) and CGP 20712A (0.1 microM). Remaining responses were blocked by compounds exhibiting affinity for atypical beta adrenoceptors, (-)-alprenolol (3 microM) and nadolol (300 microM), as well as the agonist (-)-isoproterenol (10 microM; to saturate the atypical beta adrenoceptor). However, relaxations to papaverine were unaffected by these treatments. Experiments revealed that potential cotransmitters (ATP, neuropeptide Y and somatostatin) do not appear to play a detectable role in relaxations produced by para-arterial sympathetic nerve stimulation. The results demonstrate, for the first time, that atypical beta adrenoceptors in guinea pig ileum receive a noradrenergic innervation.
间接证据表明豚鼠回肠中的β1肾上腺素能受体受神经支配，但尚未确定“非典型”β肾上腺素能受体是否也接受节后交感神经支配。为了回答这个问题，进行了实验，用电刺激动脉旁交感神经元以诱发豚鼠离体回肠段的舒张。通过跨壁电场刺激诱发胆碱能“抽搐”反应或用组胺产生稳态挛缩来使回肠段产生张力。动脉旁交感神经刺激引起抽搐反应的频率依赖性抑制，这种抑制被胍乙啶阻断并被右旋苯丙胺恢复，表明是典型的去甲肾上腺素能传递。在与组胺收缩并预先用苯苄胺阻断α肾上腺素能受体的制剂中，动脉旁交感神经刺激引起频率依赖性舒张，以下β肾上腺素能拮抗剂可使其幅度减小但未消除：溴乙酰阿普洛尔薄荷脑（1微摩尔）或ICI 118,551（0.3微摩尔）和CGP 20712A（0.1微摩尔）的组合。其余反应被对非典型β肾上腺素能受体具有亲和力的化合物（-）-阿普洛尔（3微摩尔）和纳多洛尔（300微摩尔）以及激动剂（-）-异丙肾上腺素（10微摩尔；使非典型β肾上腺素能受体饱和）阻断。然而，对罂粟碱的舒张不受这些处理的影响。实验表明，潜在的共递质（ATP、神经肽Y和生长抑素）似乎在动脉旁交感神经刺激产生的舒张中不起可检测的作用。结果首次证明豚鼠回肠中的非典型β肾上腺素能受体接受去甲肾上腺素能神经支配。
