Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats

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Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats

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Title: Enhancement of [m-methoxy 3H]MDL100907 binding to 5HT 2A receptors in cerebral cortex and brain stem of streptozotocin induced diabetic rats
Author: Jackson,James; Paulose,C S
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-l-[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 (K) 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.
URI: http://dyuthi.cusat.ac.in/purl/646
Date: 1998-11-19


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