Frigo G M, Lecchini S, Marcoli M, Tonini M, D'Angelo L, Crema A
Naunyn Schmiedebergs Arch Pharmacol. 1984 Feb;325(2):145-52. doi: 10.1007/BF00506194.
The concentration-effect relationships of adrenergic agonists in inhibiting muscular tone, carbachol-induced contraction of circular muscle strips and nerve-mediated motor activity during the peristaltic reflex have been studied in intact and sympathetically denervated preparations of isolated guinea-pig colon. The order of potencies of adrenergic agonists was different for muscular and nerve-mediated effects, being clonidine greater than noradrenaline greater than methoxamine greater than isoprenaline for the inhibition of peristalsis and isoprenaline greater than noradrenaline greater than methoxamine greater than clonidine for the relaxation of circular muscle. Denervation supersensitivity was specific for the adrenergic agonists and developed both to the muscular and nerve-mediated effects, involving both alpha and beta receptors. The degree of potentiation was similar for noradrenaline and isoprenaline when measured for the muscular effects but was significantly higher for noradrenaline than for isoprenaline or methoxamine when measured for peristalsis inhibition. No potentiation could be observed for papaverine and for the muscular effects of methoxamine and phenylephrine. The increase in potency of noradrenaline ranged from a 26-fold increase for the inhibition of propulsion velocity to a 2.5-fold increase for the inhibition of carbachol-induced contraction. A much narrower range was observed for isoprenaline. Potentiation could also be observed for the inhibitory effect of noradrenaline on acetylcholine release. Clonidine was the most potent agonist against peristaltic reflex and the weakest agonist in relaxing circular muscle. Denervated preparations became subsensitive to the inhibitory effect of clonidine on peristaltic reflex. The potency of clonidine relative to noradrenaline was 488 in intact preparations and only 3.1 in denervated organs.(ABSTRACT TRUNCATED AT 250 WORDS)
在豚鼠离体结肠的完整及交感神经去支配标本中，研究了肾上腺素能激动剂在抑制肌张力、卡巴胆碱诱导的环行肌条收缩以及蠕动反射期间神经介导的运动活动方面的浓度-效应关系。肾上腺素能激动剂对肌肉和神经介导效应的效价顺序不同，抑制蠕动时可乐定＞去甲肾上腺素＞甲氧明＞异丙肾上腺素，而舒张环行肌时异丙肾上腺素＞去甲肾上腺素＞甲氧明＞可乐定。去神经超敏反应对肾上腺素能激动剂具有特异性，且对肌肉和神经介导的效应均有发生，涉及α和β受体。就肌肉效应而言，去甲肾上腺素和异丙肾上腺素的增强程度相似，但在测量对蠕动抑制时，去甲肾上腺素的增强程度显著高于异丙肾上腺素或甲氧明。对于罂粟碱以及甲氧明和去氧肾上腺素的肌肉效应，未观察到增强作用。去甲肾上腺素效价的增加范围从抑制推进速度时的26倍增加到抑制卡巴胆碱诱导收缩时的2.5倍增加。而异丙肾上腺素的增加范围则窄得多。去甲肾上腺素对乙酰胆碱释放的抑制作用也可观察到增强。可乐定是对抗蠕动反射最有效的激动剂，而在舒张环行肌方面是最弱的激动剂。去神经支配的标本对可乐定对蠕动反射的抑制作用变得不敏感。在完整标本中，可乐定相对于去甲肾上腺素的效价为488，而在去神经支配的器官中仅为3.1。（摘要截短于250词）
