Desensitization of the β-adrenergic receptor of the S49 murine lymphoma cell: Mechanism of receptor loss and recovery

K. A. Rich, R. Iyengar

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7 Scopus citations


The effect of prolonged exposure of S49 murine lymphoma cells to (-) isoprenaline on the levels of β-adrenergic receptors and the stimulatory regulatory component of adenylyl cyclase (G(s)) was investigated. Exposure of wild-type S49 cells (WT cells) to isoprenaline for 16 h resulted in an 84% decrease in β-adrenergic receptors and a 78% decrease in catecholamine-stimulated adenylyl cyclase activity. The desensitization of adenylyl cyclase was homologous since no change in stimulation by any other effectors was observed. Similar treatment of cyc- S49 cells, a mutant that lacks G(s), resulted in only a 10-15% receptor loss despite a 50% decrease in catecholamine stimulation of reconstituted adenylyl cyclase activity. By quantitative extraction of G(s) from control and isoprenaline-treated WT cell membranes and reconstitution into untreated cyc- cell membranes, it was demonstrated that the levels and behaviour of G(s) in WT cell membranes were unchanged after isoprenaline treatment, despite a substantial loss of receptors from the cell surface. The β-adrenergic receptors lost from the cell surface could not be identified in any intracellular membrane fraction. Addition of cycloheximide to the culture medium of WT cells previously treated with isoprenaline resulted in a complete blockade of the restoration of β-adrenergic receptors which was otherwise observed within 16 h after removal of the agonist. It is concluded that, in the S49 cell line, prolonged exposure to agonists results in a loss of β-adrenergic receptors by a process dependent on the presence of G(s). However, the loss of receptors is selective since under conditions where the majority of receptors are lost, there is no measurable change in the level of cell surface membrane-bound G(s). The lost receptors appear to be degraded, since the restoration of receptor levels after removal of the agonist is dependent on protein synthesis.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalJournal of Molecular Endocrinology
Issue number3
StatePublished - 1989
Externally publishedYes


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