CONTROL OF RECEPTOR SENSITIVITY AT THE MESSENGER-RNA LEVEL

Neurons are able to adjust the sensitivity of receptor-mediated processes according to the level of receptor activation. Extrapolating from our knowledge of other cellular proteins, regulation of receptor mRNA availability would provide a highly economical means of achieving this objective. Epidermal growth factor is able to induce long-lasting increases in its receptor binding by increasing receptor mRNA levels, and similar effects have been shown for other growth factors. Studies on G-protein-coupled receptors, in particular using adrenoceptor clones transfected into cultured cell lines, have shown that changes in receptor number are generally associated with an alteration in receptor mRNA content. At the neuromuscular junction, dramatic increases in nicotinic acetylcholine receptor number are achieved by activating receptor subunit gene transcription. Less information is available concerning the regulation of ligand-gated ion channels in the brain. Overall, the evidence suggests that receptor mRNA levels are frequently controlled by the degree of receptor stimulation. Receptor mRNA levels are therefore likely to be one of the most important control points for both homologous and heterologous regulation of receptor sensitivity.