Types of Opioid Receptors: Relation to Antinociception

• Published in: Philosophical transactions of the Royal Society of London. Series B, Biological sciences Biological sciences, 1985-02, Vol.308 (1136), p.291-297
• Main Authors: Kosterlitz, H. W., Paterson, S. J.
• Format: Article
• Language: English
• Subjects: Agonists; Analgesics; Animals; beta-Endorphin; Binding sites; Brain - physiopathology; Cerebellum; Endorphins - metabolism; Enkephalins - metabolism; Guinea Pigs; In Vitro Techniques; Ligands; Morphine; Opioid analgesics; Opioid peptides; Opioid receptors; Pain - physiopathology; Peptide Fragments - metabolism; Protein Precursors - metabolism; Receptors; Receptors, Opioid - metabolism; Receptors, Opioid - physiology; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu
• ISSN: 0962-8436; 0080-4622; 1471-2970; 2054-0280
• DOI: 10.1098/rstb.1985.0029

The endogenous opioid peptides are derived from three large precursors. Pro-opiocortin and proenkephalin yield [Met]enkephalin, carboxy-extended [Met]enkephalins and [Leu]enkephalin. The fragments of prodynorphin are all carboxy-extended [Leu]enkephalins. Three approaches are of importance for an analysis of the physiological functions of the different endogenous opioid peptides. First, since these peptides interact with more than one of the $\mu$-, $\delta$- and $\kappa$-binding sites and thus with their receptors, it is necessary to synthesize peptides or non-peptides, which bind to only one of the sites. As far as narcotic analgesics are concerned, morphine fulfils these conditions since it interacts almost exclusively with the $\mu$-receptor. Secondly, antagonists are required that are selective for only one of the opioid receptors, even when used in high concentrations. Finally, it is important to find circumscribed areas in the nervous system that possess only one type of opioid receptor. It is now known that in the rabbit cerebellum the opioid receptors are almost exclusively of the $\mu$-type whereas in the guinea-pig cerebellum they are almost exclusively of the $\kappa$-type.