Eswar Shankar,P N; Anu, Joseph; Paulose,C S(Department of Biotechnology, May 17, 2006)
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Abstract:
In the present study dopamine was measured in the hypothalamus, brainstem, pancreatic islets and plasma, using HPLC. Dopamine D2 receptor
changes in the hypothalamus, brainstem and pancreatic islets were studied using [3H] YM-09151-2 in streptozotocin-induced diabetic and insulintreated
diabetic rats. There was a significant decrease in dopatnine content in the hypothalamus (P<0.001), brainstem (P<0.001), pancreatic islets
(P<0.001) and plasma (P<0.00I) in diabetic rats when compared to control. Scatchard analysis of [3H] YM-09151-2 in the hypothalamus of
diabetic rats showed a significant decrease in Bax (P<0.001) and Kd, showing an increased affinity of D2 receptors when compared to control.
Insulin treatment did not completely reverse the changes that occurred during diabetes. There was a significant decrease in B,nax (P<0.01) with
decreased affinity in the brainstem of diabetic rats. The islet membrane preparation of diabetic rats showed a significant decrease (P<0.001) in the
binding of [3H] YM-09 151-2 with decreased Kd (P<0.001) compared to control. The increase in affinity of D2 receptors in hypothalamus and
pancreatic islets and the decreased affinity in brainstem were confirmed by competition analysis. Thus our results suggest that the decreased
dopamine D, receptor function in the hypothalamus, brainstem and pancreas affects insulin secretion in diabetic rats, which has immense clinical
relevance to the management of diabetes.
Jackson,James; Paulose,C S(Department of Biotechnology, November 19, 1998)
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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.