Alpha2 adrenergic and high affinity serotonergic receptor changes in the drain stem of streptozotocin-induced diabetic rats

LIFE SCIENCES

卷:65

Article

Padayatti, PS ; Paulose, CS

关键词: brain stem;    streptozotocin-diabetes;    adrenergic receptors;    serotonergic receptors;   

DOI  :  10.1016/S0024-3205(99)00261-1

来源: Elsevier

【 摘 要 】

The brain stems (BS) of streptozotocin (STZ)-diabetic rats were studied to see the changes in neurotransmitter content and their receptor regulation. The norepinephrine (NE) content determined in the diabetic brain stems did not show an increase, while epinephrine (EPI) content increased significantly compared with control. The NE to EPI turnover showed a significant increase. The alpha(2) adrenergic receptor kinetics revealed that the receptor affinity was significantly reduced during diabetes. In insulin heated rats the NE content decreased while EPI content remained increased as in the diabetic state. Insulin treatment increased the B-max for alpha(2) adrenergic receptors significantly while the increase in Kd reversed to normal. Unlabelled clonidine inhibited [H-3]NE binding in BS of control, diabetic and insulin treated diabetic rats showed that alpha(2) adrenergic receptors consisted of two populations of binding sites with Hill slopes significantly away from unity. In diabetic animals the ligand bound weaker to the low affinity site than in controls. Insulin treatment reversed this alteration to control levels. The displacement analysis using (-)-epinephrine against [H-3]yohimbine in control and diabetic animals revealed two populations of receptor affinity states. In control animals, when GTP analogue added with epinephrine, the curve fitted for a single affinity model; but in the diabetic BS this effect was not observed. In both the diabetic and control BS the effects of monovalent cations on affinity alterations were intact. Our data thus show that alpha(2) adrenergic receptors have a reduced affinity due to an altered post receptor affinity regulation. The serotonin (5-HT) content in the brain stem increased. Its precursor (5-hydroxy) tryptophan (5-HTP) showed an increase and its breakdown metabolite (5-hydroxy) indoleacetic acid (5-HIAA) showed a significant decrease. This showed that in serotonergic nerves there is a disturbance in both synthetic and breakdown pathways which lead to an increased 5-HT. The high affinity serotonin receptor numbers remained unaltered with a decrease in the receptor affinity. The insulin treatment reversed these altered serotonergic receptor kinetic parameters to control level. Thus our study shows a decreased serotonergic receptor function. These changes in adrenergic and serotonergic receptor function were suggested to be important in insulin function during STZ diabetes.

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