Analgesia and opioid receptors pharmacological, regulation of associated transduction | Analgesia y receptores opioides: Regulacion farmacologica de la transduccion asociada

Abstract

Mu and delta opioid receptors, as well as α2 adrenoceptors regulate different G proteins in the cell membrane. In the present work, the function of the class Gi2, which is regulated by all these receptors, was impaired by using icy pertussis toxin or an oligodeoxynucleotide (ODN) to a base sequence of the Gi2α gene. In mice undergoing either treatment, morphine (μ- agonist), [DPen2,5]enkephalin (DPDPE) (δ-agonist) and clonidine (α2- adrenergic agonist) were less effective at producing antinociception. The icv injection of myristoyl Gi2α subunits restored the analgesic potency of the agonists. This result indicates the entrance and functional coupling of these subunits to the G receptors. In mice treated with the irreversible blocker of μ-receptors, β-funaltrexamine (β-FNA), or in animals undergoing subchronic treatment with increasing doses of an ODN to a base sequence of the μ- receptor gene, the injection of Gi2α subunits did not improve the effect of the agonists. Neither did this treatment alter the effect of the analgesic substances in mice which had previously undergone no treatment. This observation indicates that, in normal conditions, receptors and G proteins are optimally packed in the membrane, and that exogenous Gα subunits do not contribute to their effect.