Gunst S J, Stropp J Q, Flavahan N A
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minnesota 55905.
J Appl Physiol (1985). 1989 Sep;67(3):1294-8. doi: 10.1152/jappl.1989.67.3.1294.
The possibility that differences in beta-adrenergic sensitivity among canine trachealis muscles contracted with different contractile agonists are related to differences in the receptor-occupancy characteristics of the contractile agonists was investigated. Relaxation to isoproterenol was compared in muscles contracted with the muscarinic agonists McN-A-343 and acetylcholine (ACh). The apparent dissociation constant (pKB) values for the M1-antagonist, pirenzepine, against ACh (6.96 +/- 0.18) and McN-A-343 (6.84 +/- 0.08) were similar. The pKB values for the M3-antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) against ACh (8.76 +/- 0.13) and McN-A-343 (8.71 +/- 0.10) were also similar, suggesting that these agonists were activating the same subtype of muscarinic receptor, probably M3. However, the contractile response to ACh was associated with a greater receptor reserve than that for McN-A-343. Isoproterenol relaxed muscles contracted with McN-A-343 much more effectively than those contracted with an equieffective concentration of ACh. The results suggest that the relative resistance of ACh-induced contractions to relaxation by isoproterenol may not be an inherent quality of muscarinic receptor stimulation. The large receptor reserve available to ACh may act to buffer the contractile response from the inhibitory effects of beta-adrenergic stimulation. Alternatively, ACh may be able to initiate subcellular mechanisms that are unavailable to agonists of lower efficacy.
研究了犬气管肌在与不同收缩激动剂收缩时β-肾上腺素能敏感性差异与收缩激动剂受体占据特性差异之间的关系。比较了用毒蕈碱激动剂 McN-A-343 和乙酰胆碱（ACh）收缩的肌肉对异丙肾上腺素的舒张反应。M1 拮抗剂哌仑西平对 ACh（6.96±0.18）和 McN-A-343（6.84±0.08）的表观解离常数（pKB）值相似。M3 拮抗剂 4-二苯基乙酰氧基-N-甲基哌啶甲基碘化物（4-DAMP）对 ACh（8.76±0.13）和 McN-A-343（8.71±0.10）的 pKB 值也相似，表明这些激动剂激活的是同一亚型的毒蕈碱受体，可能是 M3。然而，对 ACh 的收缩反应比 McN-A-343 具有更大的受体储备。异丙肾上腺素对用 McN-A-343 收缩的肌肉的舒张作用比对用等效应浓度的 ACh 收缩的肌肉更有效。结果表明，ACh 诱导的收缩对异丙肾上腺素舒张的相对抗性可能不是毒蕈碱受体刺激的固有特性。ACh 可用的大量受体储备可能起到缓冲β-肾上腺素能刺激抑制作用的收缩反应的作用。或者，ACh 可能能够启动低效能激动剂无法启动的亚细胞机制。
