Functional Evolution of Opioid Family G Protein-Coupled Receptors

Opioid receptors are a family of receptors that belong to the type A GPCR group. Opioid receptors mediate a large myriad of physiological responses in different vertebrate species. There is evidence for the existence of opioid receptors from very early in evolution, and here we discuss a possible evolutionary path for their development. The physiological characteristics of the endogenous opioid system as well as the biochemical and pharmacological properties of these receptors are analyzed from an evolutionary viewpoint. Bioinformatic analysis from several groups supports the double whole-genome duplication (2R) theory, which in the case of the opioid receptor family resulted in the formation of four opioid receptors from one common ancestral gene. In the present chapter, we show the existence of a correlation between the bioinformatic analyses, the physiological characteristics, and the biochemical analyses of opioid receptors from different species throughout vertebrate evolution. The comparative pharmacological and biochemical analysis of opioid receptors from different species supports our hypothesis of the mechanism of an evolutionary vector that increases type selectivity of opioid receptors. The current literature provides experimental support to the evolutionary model that is derived from bioinformatics. According to this model, mu and delta opioid receptors share a common ancestral origin, and the mu opioid receptor exhibits positive selection and an accelerated rate of molecular evolutionary. Comparative pharmacology and biochemistry also provide functional links between the kappa opioid receptor and the nociceptin/orphanin FQ receptor (NOP) that suggests a common ancestral origin, further supporting the 2R theory applied to the family of opioid receptors.