Influence of opioids on beta-receptors down-regulation: studies in cultured C6 glioma cells.

Opioids' modulation of beta-receptors' density and function has been investigated in a cultured cell line system. Rat C6 glioma cells do not have opioid receptors or, at least, the number of these receptors is very low, but cell exposure to desmethylimipramine (DMI) causes expression of functional opioid receptors as indicated by the increased [3H]DHM binding and by the acquired ability of opioids to inhibit ISO-stimulated cAMP accumulation. Cell exposure to DMI also causes beta-receptors' down-regulation as indicated by the decline in [3H]DHA binding coupled to a reduced ability of isoproterenol (ISO) to stimulate cAMP accumulation in intact cells. In the present paper we show that cell exposure to opioid agonists during DMI treatment counteracted DMI-induced beta-receptor loss. Similarly, opioid agonists added at the beginning of ISO exposure in DMI-pretreated cells, inhibited ISO-induced beta-receptor tachyphylaxis. These results suggest that opioids may exert a protective effect on beta-receptor function and this appears to be a common mechanism which is operant when overstimulation of beta-receptors takes place.