Recovery of beta-adrenergic receptors following long term exposure of astrocytoma cells to catecholamine. Role of protein synthesis.
As a part of the process of agonist-induced desensitization, 1321N1 human astrocytoma cells lose up to 95% of their beta-adrenergic receptors, as detected by 125I-hydroxybenzylpindolol (125IHYP) binding, after 12-24 h of exposure to isoproterenol. In preconfluent cultures the loss of beta-receptors is completely reversible upon removal of isoproterenol, with receptor levels reaching 100% of control levels within 48-72 h. Addition of cycloheximide (5 micrograms/ml) upon removal of agonist does not prevent the recovery of receptors. After an initial 4-h lag, receptors accumulate in the presence of cycloheximide until the same receptor level is reached that was present at the onset of desensitization. Confluent cultures, which have a reduced number of receptors per cell, recover beta-receptors to only 60 to 70% of control levels following removal of isoproterenol. In addition, cycloheximide blocks the recovery of receptors in these cultures. The effects of cycloheximide on the accumulation of receptors during cell growth suggest that receptors are stable in preconfluent cultures and that turnover only occurs later when cultures are confluent. The data also indicate that long term exposure of cells to catecholamine results in a form of the beta-adrenergic receptor that is undetectable by 125IHYP binding but, nonetheless, retains its primary amino acid structure. The undetectable receptors appear to be retained until agonist is removed, whereupon they become detectable by 125IHYP binding with a t1/2 of about 36 h in the presence of cycloheximide.
D001254:Astrocytoma / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D009363:Neoplasm Proteins; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; C011878:iodohydroxybenzylpindolol; D003513:Cycloheximide; D010869:Pindolol; D007545:Isoproterenol