The beta-adrenergic receptors are members of the G-protein-linked receptor family including adrenergic, muscarinic, dopaminergic, opiate, and serotonergic receptors. We are investigating the mechanism by which cells regulate the level of their own beta-adrenergic receptors in response to stimulation of these receptors in the rat glioma cell line C6. We have found that control of the levels of messenger RNA needed to make new receptor protein is complex and occurs at several levels. Transcription of new MRNA coding for the receptor protein is paradoxically increased (in one subtype and possibly both) at a time when total receptor MRNA and protein begins to decrease. Inherent stability of receptor mRNA is not changed by receptor stimulation. The observed down-regulation of receptor MRNA appears to require protein synthesis, because protein synthesis inhibitors block receptor MRNA degradation. The balance of tonic stimulation and inhibition of intracellular CAMP level from stimulatory and inhibitory G-proteins plays a key role in regulating transcription of new MRNA coding for the receptor protein. The study of the regulation of receptor levels on cells provides insight into the regulation of neuronal sensitivity to natural transmitters and drugs designed to block these transmitters, as well as insight into one mode by which external signals are transmitted to the nucleus. The adrenergic receptors have been implicated in hyperthyroidism and depression.
