Distribution of nicotinic receptors in cynomolgus monkey brain and ganglia: localization of alpha 3 subunit mRNA, alpha-bungarotoxin and nicotine binding sites.
The distribution of nicotinic receptors in the brain and ganglia of the Cynomolgus monkey was studied by in situ hybridization and receptor autoradiography. A 35S-labeled antisense riboprobe for the mRNA of the alpha 3 subunit of the human nicotinic receptor, [3H]L-nicotine and [125]alpha-bungarotoxin were used as markers. The highest levels of alpha 3-mRNA were observed in the hippocampus, the medial habenula, the lateral geniculate, the granular layer of the cerebellum, as well as in the pineal gland; moderate levels were found in other nuclei of the thalamus and in the deeper layers of the cerebral cortex. High-affinity binding sites for [3H]L-nicotine were observed mainly in the thalamus. The distribution of [125I]alpha-bungarotoxin binding sites was different from that observed for alpha 3-mRNA and [3H]L-nicotine; they were most abundant in a few specific thalamic nuclei, in the medial habenula and in lamina I of the cerebral cortex. The localization of these three markers was also investigated in the sympathetic, parasympathetic and sensory ganglia of the monkey. Intense labeling was observed for alpha 3-mRNA and for [125I]alpha-bungarotoxin in the sympathetic and parasympathetic ganglia, whereas no positive signal was seen in the ganglion of Gasser. [3H]L-nicotine binding was not detected in any of the ganglia examined. High levels of mRNA for the alpha 3 subunit of the nicotinic receptor were also detected in human sympathetic ganglia. Comparison between alpha 3-mRNA distribution and [3H]L-nicotine binding suggests that in the Cynomolgus monkey brain, the alpha 3 subunit may participate in the formation of more than one nicotinic receptor subtype: a high-affinity binding site for [3H]L-nicotine in the thalamus, and other sites with low affinity for nicotine in the medial habenula and cerebral cortex. Both the alpha 3-mRNA and the [125I]alpha-bungarotoxin are highly expressed in the sympathetic ganglia; however, since no information is presently available on the intraneuronal cellular localization, it cannot be established whether or not they are both present at synaptic sites.
Cimino
M
M
Institute of Pharmacology and Pharmacognosy, University of Urbino, Italy.
Marini
P
P
Fornasari
D
D
Cattabeni
F
F
Clementi
F
F
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002038:Bungarotoxins / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008252:Macaca fascicularis; D046911:Macromolecular Substances; D009538:Nicotine / Q000378:metabolism; D009928:Organ Specificity; D010870:Pineal Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D013233:Stellate Ganglion / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism*; D014316:Tritium; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579167:Chrna7 protein, human; D007457:Iodine Radioisotopes; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014316:Tritium; D009538:Nicotine