Regulation by 8-Br-cAMP of beta-adrenoceptors in cultured myocardial cells.
Primary cultures of myocardial cells from neonatal rats were exposed for up to 5 days to the cyclic AMP derivative 8-Br-cAMP. After one day of exposure to the nucleotide, an increase in specific binding capacity of the hydrophilic beta-adrenoceptor antagonist 3H-CGP 12177 was observed in intact cells. (-)-Isoprenaline displaced the radioligand from its binding site. Neither the KD of the antagonist, nor that of the agonist were significantly affected by 8-Br-cAMP. The loss of beta-adrenoceptors during desensitization by long term treatment of the cells with isoprenaline could be partially prevented by 8-Br-cAMP. Only in desensitized, but not in normal cells was isoprenaline-induced cAMP formation significantly enhanced by 8-Br-cAMP pretreatment. This may indicate that beta-adrenoceptors which appear during 8-Br-cAMP exposure are poorly coupled to the adenylate cyclase. Alternatively, the change in receptor density may be accompanied by alterations of other components in the beta-adrenergic system, e.g. an inhibition of the adenylate cyclase. We suggest that cAMP-dependent feed-back regulation of the beta-adrenergic system may play a role during postnatal myocardial differentiation.
Reuter
H
H
Porzig
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D007545:Isoproterenol; C033394:CGP 12177