Changes in beta-adrenoceptor binding properties and receptor-cyclase coupling during in vitro maturation of rat reticulocytes.
The loss of beta-adrenergic responsiveness during reticulocyte maturation was studied under tissue culture conditions in a defined cell population from rats. Initial beta-receptor density and receptor-mediated cAMP formation in culture medium (RPMI 1640) exceeded the values obtained in isotonic KC1-buffer by 56 and 120% respectively. During cell cultivation receptor density and hormonal responsiveness decreased rapidly by 40-50% of their initial values within the first 20 h. In the following 3 days the rate of loss varied between 10 and 15%/d. The same time course was observed for the maturation-dependent decrease in forskolin-stimulated cAMP formation. ATP depletion of cultivated cells caused a complete and irreversible loss of cAMP response within 90 min. Our results indicate that cell metabolism regulates the strength of the hormonal response. A defect in adenylate cyclase or in cyclase N-protein interaction seems to be rate-limiting for the functional inactivation of the beta-adrenergic system during reticulocyte maturation.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D004082:Dihydroalprenolol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012156:Reticulocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C033394:CGP 12177