Decreased [3H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin-induced diabetic rats

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.

Enhanced Dopamine D1 and D2 Receptor Gene Expression in the Hippocampus of Hypoglycaemic and Diabetic Rats

“…Yamato et al (2004) and Kino et al (2004) reported that diabetes mellitus decreases the DA release from the hippocampus in both experimentally and spontaneously diabetic rats. Previous studies from our laboratory reported a decrease in plasma DA concentration, which indicates that diabetes causes an alteration in the overall dopaminergic function and activity (Shankar et al 2007). The turnover rate of DA to HVA showed a significant increase in the hippocampus of diabetic, diabetic ?IIH and control ?IIH rats indicating an increase in the DA metabolism.…”

Hormonal Signaling Systems of the Brain in Diabetes Mellitus

“…The treatment with insulin or curcumin, an active component in rhizome of Curcuma longa, reduced DM-induced alteration of D 1 -and D 2 -DARs in the cerebral cortex and increased D 1 -DAR expression in the cerebellum to near control, thereby improving the cognitive and emotional functions associated with these regions. In the hypothalamus and brainstem of STZ rats a significant decrease in the DA content and the number of D 2 -DARs, and an increase in affinity of the latter were found, and the insulin therapy did not completely reverse the DM-induced changes of D 2 -DAR functions (Shankar et al, 2007). The hypothalamus and brainstem are two parts of the brain very important for monitoring the glucose status and the regulation of feeding.…”

Enhanced 5-HT2A Receptor Status in the Hypothalamus and Corpus Striatum of Ethanol-Treated Rats

“…An enhanced 5-HT 2A receptor status in hypothalamus and corpus striatum was observed. The functional regulation of the central GABA and 5-HT 2 receptors during liver regeneration (Sudha and Paulose 1998;Biju et al 2001Biju et al , 2002Pyroja et al 2007), decreased alpha1-adrenergic receptor binding in the cerebral cortex and brain stem during pancreatic regeneration (Ani et al 2006) and decreased dopamine D 2 receptor binding in the hypothalamus and brain stem of streptozotocindiabetic rats (Shankar et al 2007) were reported form our lab. The cerebral cortex and brainstem DA D 2 functional regulation contributed to the central nervous system manifestations in ethanol-treated rats is also reported (George et al 2007).…”