Synaptic localization of kappa opioid receptors in guinea pig neostriatum.

Abstract

Distribution of K opioid receptors was examined by EM radioautography in sections of guinea pig neostriatum with the selective 12SI-labeled dynorphin analog . Most specifically labeled binding sites were found by probability circle analysis to be associated with neuronal membrane appositions. Because of limitations in resolution of the method, the radioactive sources could not be ascribed directly to either one of the apposed plasma membranes. Nevertheless, three lines of evidence favored a predominant association of ligand with dendrites of intrinsic striatal neurons: (i) the high frequency with which labeled interfaces implicated a dendrite, (il) the enrichment of dendrodendritic interfaces, and (iii) the occurrence of dendritic profiles labeled at several contact points along their plasma membranes. A small proportion of labeled sites was associated with axo-axonic interfaces, which may subserve the K opioidinduced regulation of presynaptic dopamine and acetylcholine release documented in guinea pig neostriatum. Although most membrane-associated K sites were found at extrasynaptic locations, -23% were associated with synaptic specializations. This proportion is markedly higher than that previously reported for either ,u or 6 sites in rat neostriatum. Whether labeled synapses represent preferential sites of action for K ligands remains to be established. In any event, these results support the hypothesis that in mammalian brain K opioid receptors are conformationally and functionally distinct from ,u and 6 types.

Electron Microscopic Distribution of Mu Opioid Receptors on Noradrenergic Neurons of the Locus Coeruleus

“…To compensate for these limitations in resolution, we resorted to a statistical assessment of silver grain distribution derived from the resolution circle method originally described by Williams (1969), which involves comparing the distribution of autoradiographic grains with that of a hypothetical population of randomly distributed grains. As in our earlier studies of the ultrastructural distribution of opioid receptors in the neostriatum Beaudet, 1984a,b, 1987;Jomary et al, 1992) and of neurotensin receptors in the ventral midbrain (Dana et al, 1989), this method made it possible to differentiate intracellular (exclusive grains) from membrane-associated (shared grains) binding sites. Furthemore, its combination here with 6-OHDA lesion experiments allowed us to sPecifically ascribe shared grains to radioactive sources associated with noradrenaline cells.…”

“…This approach was chosen because it permits high-sensitivity detection of sites of ligand recognition and lends itself to quantification of receptor densities along neuronal plasma membranes (Beaudet, 1993). It also made it possible to compare the subcellular distribution of mu opioid receptors in the LC with that of mu, delta and kappa opioid receptors visualized by the same method in other brain regions Beaudet, 1984b, 1987;Jomary et al, 1992;Pasquini et al, 1992). Finally, through combination with tyrosine hydroxylase immunohistochemistry and 6-hydroxydopamine (6-OHDA) lesioning techniques, it allowed a quantitative assessment of their pre-versus postsynaptic localization in the LC.…”

Dynorphin‐immunoreactive terminals in the rat nucleus accumbens: Cellular sites for modulation of target neurons and interactions with catecholamine afferents

“…These results suggest a similar presynaptic role for DYN modulation of other transmitters in the Acb. Presynaptic interactions between terminals containing DYN and other axons is supported by the autoradiographic localization of kappa receptors to interfaces between axons (Jomary et al, 1992). Many of the noted appositions between DYN axon terminals and other unlabeled axons occurred on the preterminal portion of the unlabeled axon.…”

Presynaptic and postsynaptic subcellular localization of substance P receptor immunoreactivity in the neostriatum of the rat and rhesus monkey (Macaca mulatta)

“…There is also evidence for presynaptic glutamate receptors on dopamine axons (Wang, 1991) and dopamine receptors on cortical terminals (Maura et al, 1989). Concerning opioid receptors, 23% of K sites, < 10% of p sites, and 2% of 6 sites have been reported to be associated with synaptic specializations in guinea pig neostriatum (Hamel and Beaudet, 1984;Jomary et al, 1992). Collectively, these results indicate that individual axon terminals containing receptors for multiple neurotransmitters may be a general phenomenon of synapses in the brain.…”