Johansson L H
Preclinical Research and Development Department, Astra Draco AB, Lund, Sweden.
J Pharmacol Toxicol Methods. 1992 Sep;28(2):107-12. doi: 10.1016/1056-8719(92)90055-6.
The binding, adenylate cyclase activation, and functional effect of four beta-adrenoceptor agonists were studied in the guinea-pig lung parenchyma preparation and the results were compared with those obtained earlier in guinea-pig left-heart ventricle (beta 1-adrenoceptors) and soleus muscle (beta 2-adrenoceptors) preparations. The pKi-values of the unselective compounds, isoprenaline and orciprenaline, were in good agreement with those obtained in the heart and soleus muscle. The beta 2-adrenoceptor selective compounds KWD 2026 and terbutaline were bound to two sites, one corresponding to the beta 1-adrenoceptors and the other to the beta 2-adrenoceptors. The pKi-value of isoprenaline was in good agreement with its pKact-value indicating that maximum adenylate cyclase activity is obtained when the occupancy of the receptors is maximal. Further, the relative intrinsic efficacy calculated from the functional effect and receptor occupancy agreed well with the relative maximum adenylate cyclase activation by the agonists which was also found earlier for the guinea-pig heart ventricle and soleus muscle preparations. Relative effects were obtained from both functional experiments and from affinity and adenylate cyclase activating studies. There was good agreement between relative effects obtained in these two ways. It is concluded that the guinea-pig lung parenchyma preparation may be useful for the study of the beta-adrenoceptor adenylate cyclase system.
在豚鼠肺实质制备物中研究了四种β-肾上腺素能受体激动剂的结合、腺苷酸环化酶激活及功能效应，并将结果与先前在豚鼠左心室（β1-肾上腺素能受体）和比目鱼肌（β2-肾上腺素能受体）制备物中获得的结果进行比较。非选择性化合物异丙肾上腺素和奥西那林的pKi值与在心脏和比目鱼肌中获得的值高度一致。β2-肾上腺素能受体选择性化合物KWD 2026和特布他林与两个位点结合，一个对应β1-肾上腺素能受体，另一个对应β2-肾上腺素能受体。异丙肾上腺素的pKi值与其pKact值高度一致，表明当受体占有率最大时可获得最大的腺苷酸环化酶活性。此外，根据功能效应和受体占有率计算的相对内在效能与激动剂的相对最大腺苷酸环化酶激活高度一致，这在先前豚鼠心室和比目鱼肌制备物中也已发现。相对效应可从功能实验以及亲和力和腺苷酸环化酶激活研究中获得。通过这两种方式获得的相对效应高度一致。结论是豚鼠肺实质制备物可能有助于β-肾上腺素能受体腺苷酸环化酶系统的研究。
