THE BETA(2)-ADRENERGIC RECEPTOR - STUDY MODEL FOR AGONIST-INDUCED DESENSITIZATION

Approximately 80 % of known hormones and neurotransmitters mediate their effects through the activation of G protein linked receptors. Propagation of the signal via these receptors is under the control of tight regulatory processes which confer high degrees of plasticity to these transduction pathways. In particular, desensitization of many receptors is known to occur in response to their own activation or following stimulation of other signalling pathways. Such desensitization can be extremely rapid (seconds-minutes) and transient or else can develop slowly (hours-days) over the course of sustained stimulation. Over the last few years, the molecular mechanisms underlying these regulatory processes have slowly begun to be unravelled and are known to involve post-translational modifications of the receptors as well as gene expression regulation. In this review, we have used the beta(2)-adrenergic receptor, which can be considered in many instances as prototypical of the G protein-coupled receptors, as a model to describe the various mechanisms contributing to agonist-promoted ;desensitization, Although, receptor-specific mechanisms undoubtedly exist, those described for the beta(2)-adrenergic receptor form the basis for a general model which can be used as a framework for the study of the regulation of other G protein-coupled receptors.