New Antibodies for Opioid Receptor Research

Opioid peptides are endogenous neuromodulators that play a major role in nociception by interacting with several membrane receptors. Molecular cloning techniques have characterized the nucleotide sequence of several distinct opioid receptors, including the d-, k- and m-opioid receptors.¹ The cloned receptors are highly homologous (65%), differing only at the N- and C-termini and at the extracelluar loops that confer binding specificity.² All three receptors interact with heterotrimeric G proteins.³

d-Opioid receptors (DOR) are located postsynaptically on pallidostriatal feedback neurons.⁴ DORs also modulate nociception presynaptically in the periaqueductal gray where immunolabeling of DOR has been shown to be intracellular and often associated with large dense-core vesicles. ⁵ Additionally, receptor autoradiographic investigations have localized DORs to the external plexiform layer of the olfactory bulb, the nucleus accumbens, several layers of the cerebral cortex and several nuclei of the amygdala.⁶

The k-opioid receptor (KOR)⁷ is primarily responsible for mediating the effects of the products of preprodynorphin and possibly preproenkephalin.⁸ Localization of the KOR is primarily postsynaptic. Immunolocalization of KOR on sections of rat and guinea-pig brain demonstrated prominent staining in the ventral forebrain, hypothalamus, thalamus, posterior pituitary and midbrain.⁸

Of the three opioid receptors, the m-opioid receptor (MOR) shows the highest affinity for morphine. Activation of MORs inhibits GABA-containing interneurons, resulting in a net excitatory effect in the hippocampus.⁹ Localization of MORs is both pre- and post-synaptic and almost exclusively on GABAergic interneurons. MORs are widely distributed in regions throughout the brain and spinal cord including laminae I and II of the medullary and spinal dorsal horns, the striatum, the optic tract and the locus coeruleus.¹⁰

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