title: Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats.
abstract: 5-Hydroxytryptamine2A (5-HT2A) receptor kinetics was studied in cerebral cortex and brain stem of streptozotocin (STZ) induced diabetic rats. Scatchard analysis with [3H] (+/-) 2,3dimethoxyphenyl-1-[2-(4-piperidine)-methanol] ([3H]MDL100907) in cerebral cortex showed no significant change in maximal binding (Bmax) in diabetic rats compared to controls. Dissociation constant (Kd) of diabetic rats showed a significant decrease (p < 0.05) in cerebral cortex, which was reversed to normal by insulin treatment. Competition studies of [3H]MDL100907 binding in cerebral cortex with ketanserin showed the appearance of an additional low affinity site for 5-HT2A receptors in diabetic state, which was reversed to control pattern by insulin treatment. In brain stem, scatchard analysis showed a significant increase (p < 0.05) in Bmax accompanied by a significant increase (p < 0.05) in Kd. Competition analysis in brain stem also showed a shift in affinity towards a low affinity State for 5-HT2A receptors. All these parameters were reversed to control level by insulin treatment. These results show that in cerebral cortex there is an increase in affinity of 5-HT2A receptors without any change in its number and in the case of brain stem there is an increase in number of 5HT2A receptors accompanied by a decrease in its affinity during diabetes. Thus, from the results we suggest that the increase in affinity of 5-HT2A receptors in cerebral cortex and upregulation of 5-HT2A receptors in brain stem may lead to altered neuronal function in diabetes.
authors.affiliation: Molecular Neurobiology and Cell Biology Unit, Department of Biotechnology, Cochin University of Science and Technology, Kerala, India.
authors.forename: J
authors.initials: J
authors.lastname: Jackson
authors.forename: C S
authors.initials: CS
authors.lastname: Paulose
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D005464:Fluorobenzenes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010880:Piperidines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism; D013311:Streptozocin; D014316:Tritium
chemical_list: D005464:Fluorobenzenes; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014316:Tritium; D013311:Streptozocin; C079049:volinanserin