The brain neurotransmitters' receptor activity and hormonal pathways control many physiological functions in the body. Acetylcholine (ACh), a major neurotransmitter from autonomic nervous system, regulates the cholinergic stimulation of insulin secretion, through interactions with muscarinic receptors. The objective of the present study was to investigate the changes in the total muscarinic and muscarinic M1 receptor ([(3)H]quinuclidinyl benzilate; QNB) binding and gene expression in the hypothalamus, brainstem, and pancreatic islets of streptozotocin (STZ)-induced diabetic and insulin-treated diabetic rats. In the hypothalamus and brainstem, total muscarinic receptor numbers were increased in diabetic rats with increase in affinity. Hypothalamic and brainstem muscarinic M1 receptors number were decreased in STZ diabetic rats with increase in affinity. In the pancreatic islets, muscarinic M1 receptors of diabetic rats were decreased, with a decrease in affinity. In all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR data also showed a decrease in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. Thus our results suggest that insulin modulates binding parameters and gene expression of total and muscarinic M1 receptors.

The present study was to investigate the role of central 5-HT and 5-HT(1A) receptor binding and gene expression in a rat model of pancreatic regeneration using 60% pancreatectomy. The pancreatic regeneration was evaluated by 5-HT content and 5-HT(1A) receptor gene expression in the cerebral cortex (CC) and brain stem (BS) of sham operated, 72 h and 7 days pancreatectomised rats. 5-HT content significantly increased in the CC (P < 0.01) and BS (P < 0.05) of 72 h pancreatectomised rats. Sympathetic activity was decreased as indicated by the significantly decreased norepinephrine (NE) and epinephrine (EPI) level (P < 0.001 and P < 0.05) in the plasma of 72 h pancreatectomised rats. 5-HT(1A) receptor density and affinity was decreased in the CC (P < 0.01) and BS (P < 0.01). These changes correlated with a diminished 5-HT(1A) receptor mRNA expression in the brain regions studied. Our results suggest that the brain 5-HT through 5-HT(1A) receptor has a functional role in the pancreatic regeneration through the sympathetic regulation.

In the present study we investigated the role of 5-hydroxytryptamine (5-HT) and 5-HT1A receptor during liver regeneration after partial hepatectomy (PH) and N-nitrosodiethylamine (NDEA) induced hepatocellular carcinoma in male Wistar rats. 5-HT content was significantly increased during liver regeneration after PH and NDEA induced hepatocellular carcinoma. Scatchard analysis using 8-OH-DPAT, a 5-HT1A specific agonist showed a decreased receptor during liver regeneration after PH and NDEA induced hepatocellular carcinoma. 5-HT when added alone to primary hepatocyte culture did not increase DNA synthesis but was able to increase the EGF mediated DNA synthesis and inhibit the TGF beta 1 mediated DNA synthesis suppression in vitro. This confirmed the co-mitogenic activity of 5-HT. 8-OH-DPAT at a concentration of 10(-4) M inhibited the basal and EGF-mediated DNA synthesis in primary hepatocyte cultures. It also suppressed the TGF beta 1-mediated DNA synthesis suppression. This clearly showed that activated 5-HT1A receptor inhibited hepatocyte DNA synthesis. Our results suggest that decreased hepatic 5-HT1A receptor function during hepatocyte regeneration and neoplasia has clinical significance in the control of cell proliferation.

Our results suggest that the decreased serotonin function mediated through 5-HT(2A) receptors have a regulatory role on ALDH activity. This will have clinical significance to correct alcoholics from addiction due to allergic aldehyde accumulation.

Ethanol exerts numerous pharmacological effects through its interaction with various neurotransmitters. The dopaminergic pathway is associated with cognitive, endocrine, and motor functions, and reinforcement of addictive substances or behaviours. Aldehyde dehydrogenase (ALDH) is a vital enzyme involved with alcohol metabolism and detoxification. In the present study, we investigated the role of cerebral cortex and brain stem dopamine D(2) receptors in the functional regulation on ALDH enzyme activity, in ethanol administrated rats. Two groups of rats were selected viz. control and alcoholic. Cerebral cortex, brain stem and the liver dopamine content was decreased significantly (P < 0.05, 0.05, 0.001, respectively) and homovanillic acid/dopamine (HVA/DA) ratio has significantly increased (P < 0.05, 0.001 and 0.001), respectively in ethanol treated rats when compared to control. Scatchard analysis of [(3)H]YM-09151-2 binding to synaptic membrane preparations of cerebral cortex and brain stem showed a significant decrease (P < 0.001, 0.05, respectively) in B (max) in ethanol treated rats compared to control and the K (d) also decreased significantly (P < 0.05). The ALDH analysis showed a significant increase (P < 0.05) in V (max) in cerebral cortex, plasma and liver of experimental rats when compared with control without having significant change in brain stem but with decreased K (m) (P < 0.001). Our results suggest that decreased function of dopamine mediated through DA D(2) receptor in the cerebral cortex and brain stem enhanced the brain, plasma and liver ALDH activity in ethanol treated rats. This ALDH regulation has significance to correct alcoholics from addiction due to allergic reaction observed in aldehyde accumulation.