The use of the guinea-pig lung parenchyma preparation in studies of the beta-adrenoceptor adenylate cyclase system.
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.
Preclinical Research and Development Department, Astra Draco AB, Lund, Sweden.
L H
LH
Johansson
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism; D008024:Ligands; D008168:Lung / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; C033394:CGP 12177