Characterization of agonist-induced internalization and down-regulation of beta-adrenergic receptors in isolated rat lung and heart preparations.
Using isolated lung and heart preparations from male Sprague-Dawley rats, this study characterizes whether the beta-adrenergic receptor (BAR) agonist isoproterenol (ISO) can induce internalization and down-regulation of BAR in these tissues. The results showed that ISO-induced BAR internalization was time- and concentration-dependent in the lung preparations. When the lung and heart preparations were compared, however, the same ISO (10 microM, 30 min) treatment only induced BAR internalization in the lung but not in the heart preparations. Pretreatment of hypertonic sucrose medium (0.45-0.6 M) for 30 min inhibited about 50% of ISO-induced BAR internalization in the lung preparations. Treatment of either ISO (10 microM) or terbutaline (10 microM) for 3 hr or 12 hr did not significantly decrease the number of BAR in both tissue preparations. However, ISO (10 microM, 12 hr) increased the KD value of the radioligand [125I]-iodocyanopindolol for BAR in the heart homogenates. This ISO-induced KD change was not observed in the presence of cycloheximide (20 micrograms/ml), a protein synthesis inhibitor. In the presence of cycloheximide (20 micrograms/ml), ISO also did not decrease the BAR number in either tissue preparation.
Liao
J F
JF
Department & Institute of Pharmacology, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China.
Change
H T
HT
Chen
C F
CF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003513:Cycloheximide / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006982:Hypertonic Solutions / Q000494:pharmacology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011412:Propanolamines / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D006982:Hypertonic Solutions; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013395:Sucrose; D020120:Iodocyanopindolol; D003513:Cycloheximide; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol; D013726:Terbutaline; C033394:CGP 12177