enkephalin--leucine-2-alanine and naloxazone

In addition to morphine-selective mu 2 and enkephalin-preferring delta sites, recent evidence supports the presence within the central nervous system of a common site with very high affinity for both enkephalins and opiates termed the mu 1 site. This concept of a common, very high affinity site for multiple neurotransmitters is a unique concept in neuropharmacology, differing from classical transmitter systems which possess multiple receptor classes for a single transmitter. This review will address both the biochemical and pharmacological evidence supporting the existence of this site.

Topics: Aging; Analgesia; Animals; Autoradiography; Binding, Competitive; Brain; Dihydromorphine; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Ethylmaleimide; Morphine; Naloxone; Neurotransmitter Agents; Phylogeny; Receptors, Opioid; Receptors, Opioid, mu; Respiration; Substance-Related Disorders; Tissue Distribution

Topics: Analgesia; Animals; Binding, Competitive; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Kinetics; Mice; Morphine; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Respiration

Receptor binding experiments with masking of mu- and delta-receptors in the presence of an excess of unlabelled dihydromorphine and [D-Ala2, D-Leu5]enkephalin have been carried out. They indicate that 12 to 17% of original high affinity binding of [3H]Mr 2034 [-)(1R,5R,9R,2"S)-5,9-dimethyl-2-tetrahydrofurfuryl-2'-hydroxy-6, 7-benzomorphan hydrochloride), an opioid kappa-agonist, could then be detected as kappa-receptor sites in brain membranes both from untreated rats and from rats pretreated with naloxazone, too. Because of the irreversible blockade of the high affinity binding sites by naloxazone (naloxone hydrazone) treatment, the masking effects of mu- and delta-selective ligands seem to be mediated by the low affinity binding sites of these opioid receptor types. As could be shown before with [3H]Mr 2034, another kappa-agonist, [3H]bremazocine does not seem to be affected in its binding properties by naloxazone treatment of the rat in vivo. Displacement studies with several opioid agonists and antagonists, [3H]Mr 2034 and [3H]ethylketocyclazocine as radioligands in brain membranes from naloxazone treated rats and untreated controls provided further support for the evidence of two different kappa-receptors.

Topics: Animals; Benzomorphans; Binding, Competitive; Cyclazocine; Dihydromorphine; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Ethylketocyclazocine; In Vitro Techniques; Kinetics; Male; Morphinans; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, kappa

Topics: Animals; Binding, Competitive; Brain; Cells, Cultured; Endorphins; Enkephalin, Leucine-2-Alanine; Enkephalins; In Vitro Techniques; Kinetics; Membranes; Morphine; Naloxone; Narcotic Antagonists; Rats; Receptors, Opioid