Broadley K J, Chess-Williams R G, Grassby P F
J Physiol. 1986 Apr;373:367-78. doi: 10.1113/jphysiol.1986.sp016053.
Chemical sympathectomy of guinea-pigs was induced by chronic pretreatment with 6-hydroxydopamine over a 20 day period. Control animals were sham injected with vehicle at the same times. Isolated tissues were removed from the animals and beta-adrenoceptor sensitivity assessed from cumulative concentration-response curves for isoprenaline, followed after wash-out by a partial agonist (salbutamol, ritodrine or prenalterol). The following responses were measured: increases in force and rate of contraction of left and right atria respectively, inhibition of carbachol-induced ileal contractions, relaxation of intrinsic tone of lung strips and tracheal spirals, inhibition of contractions of vas deferens and soleus muscle induced by field stimulation. Left and right atria and ileum from 6-hydroxydopamine-pretreated guinea-pigs exhibited supersensitivity to beta-adrenoceptor stimulation. This was measured as a leftwards shift of the concentration-response curve for isoprenaline and as an elevation of the partial agonist maximum response (relative to isoprenaline), when compared with tissues from sham-injected controls. The supersensitivity was assumed to be due to the loss of endogenous neurotransmitter release by chemical sympathectomy and specific for the beta-adrenoceptor. In contrast, lung strips, vas deferens and soleus muscle were not supersensitive. The responses of these tissues are thought to be mediated via beta 2-adrenoceptors whereas cardiac and ileal responses are beta 1-adrenoceptor mediated. The latter receptor subtype would therefore appear to be under the influence of sympathetic innervation, but since no supersensitivity occurred at beta 2-adrenoceptors these were presumed to be non-innervated but stimulated by circulating adrenaline. These results obtained by use of chemical sympathectomy with 6-hydroxydopamine support the contention that the physiological basis of beta-adrenoceptor subclassification is that the beta 1-subtype are innervated whereas the beta 2-subtype are non-innervated.
通过在20天内用6-羟基多巴胺进行慢性预处理，诱导豚鼠进行化学性交感神经切除术。对照动物在相同时间接受假注射，注射溶媒。从动物身上取出分离的组织，通过异丙肾上腺素的累积浓度-反应曲线评估β-肾上腺素能受体敏感性，在洗脱后用部分激动剂（沙丁胺醇、利托君或普瑞特罗）进行后续评估。测量以下反应：左右心房收缩力和收缩速率的增加、卡巴胆碱诱导的回肠收缩的抑制、肺条和气管螺旋条固有张力的松弛、场刺激诱导的输精管和比目鱼肌收缩的抑制。6-羟基多巴胺预处理的豚鼠的左右心房和回肠对β-肾上腺素能受体刺激表现出超敏感性。与假注射对照的组织相比，这表现为异丙肾上腺素浓度-反应曲线向左移动以及部分激动剂最大反应升高（相对于异丙肾上腺素）。这种超敏感性被认为是由于化学性交感神经切除术导致内源性神经递质释放丧失，并且对β-肾上腺素能受体具有特异性。相比之下，肺条、输精管和比目鱼肌没有超敏感性。这些组织的反应被认为是通过β2-肾上腺素能受体介导的，而心脏和回肠的反应是由β1-肾上腺素能受体介导的。因此，后一种受体亚型似乎受交感神经支配的影响，但由于β2-肾上腺素能受体未出现超敏感性，推测它们未受神经支配，但受循环肾上腺素刺激。使用6-羟基多巴胺进行化学性交感神经切除术获得的这些结果支持了以下观点，即β-肾上腺素能受体亚分类的生理基础是β1-亚型受神经支配，而β2-亚型未受神经支配。
