The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice.

BACKGROUND The possible role of dopamine D2 receptors located in the spinal cord in the regulation of the blood glucose level have not been investigated before. METHODS In the present study, the effect of D2 receptor agonist and antagonist administered intrathecal (it) injection on the blood glucose level were examined in the Institute of Cancer Research (ICR) mice. RESULTS We found that it injection with carmoxirole (D2 receptor agonist) caused an elevation of the blood glucose level in a dose-dependent manner. Carmoxirole-induced increase of the blood glucose was significantly attenuated by L-741,626 (D2 receptor antagonist). Previously, we indicated that intrathecal (it) treatment with 0.1 μg/5 μl pertussis toxin (PTX, a Gi/Go inhibitor) produces a hypoglycemic effect in ICR in a long-term manner. In the present study, it pretreatment with PTX for 6 days almost abolished the hyperglycemic effect induced by carmoxirole. The plasma insulin level was elevated by carmoxirole, and L-741,626 or PTX pretreatment reduced carmoxirole-induced increment of the insulin level. In addition, the plasma corticosterone level was increased by carmoxirole but it pretreatment with L-741,626 or PTX did not affect carmoxirole-induced increment of the corticosterone level. CONCLUSION Our results suggest that D2 receptors located in the spinal cord play an important role in the elevation of the blood glucose level. Spinally located inhibitory G-proteins appear to be involved in hyperglycemic effect induced by carmoxirole.