Demonstration of an Autoreceptor Modulating the Release of [3H]5-Hydroxytryptamine from a Synaptosomal-Rich Spinal Cord Tissue Preparation |
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Authors: | Philip J Monroe David J Smith |
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Institution: | Departments of Anesthesiology and Pharmacology and Toxicology, West Virginia University Medical Center, Morgantown, West Virginia, U.S.A. |
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Abstract: | A superfusion system employed to measure the K+-stimulated release of 3H]5-hydroxytryptamine (3H]5-HT, 3H]serotonin) from a synaptosomal-rich spinal cord tissue preparation was carefully characterized, then used to examine the regulation of spinal 5-HT release. Spinal 5-HT release is apparently modulated by an autoreceptor. Exogenous 5-HT depressed, in a concentration-dependent manner, the K+-stimulated release of 3H]5-HT. Similarly, lysergic acid diethylamide (LSD) produced a concentration-dependent decrease in 3H]5-HT release. Methiothepin and quipazine blocked the inhibition of release induced by exogenous 5-HT. The 5-HT2 receptor antagonists spiperone and ketanserin failed to alter the action of 5-HT at the spinal 5-HT autoreceptor. Spiperone and ketanserin were shown, however, to alter the storage of 3H]5-HT. When used in concentrations greater than 10 nM, the drugs evoked increases in basal 3H]5-HT and 3H]5-hydroxyindoleacetic acid ( 3H]5-HIAA) effluxes which were independent of the presence of calcium ions. A good agreement existed between the potencies of drugs for modifying autoreceptor function and their abilities to compete for high-affinity 3H]5-HT binding in the spinal cord (designated 5-HT1). Furthermore quipazine, in concentrations that preferentially interact with the 5-HT1B subtype, antagonized the actions of exogenous 5-HT on K+-stimulated release. Spiperone, in a concentration that approximated the affinity constant of 5-HT1A sites for the drug, was ineffective in altering the ability of exogenous 5-HT to modulate K+-stimulated 3H]5-HT release. These results suggest that 5-HT1B sites are associated with serotonergic autoreceptor function in the spinal cord. |
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Keywords: | [3H]Serotonin release Superfusion apparatus Spinal cord Spiperone Methiothepin Quipazine |
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