Pyroja, S; Paulose,C S(Department of Biotechnology, Faculty of Science, April , 2002)
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Abstract:
The work is an attempt to understand the role of 5-HT, 5-HT1A and 5-HT2C receptors in the regulation of liver cell proliferation using in vivo and in vitro models. The work also focuses on the brain serotonergic changes associated with hapatocyte proliferation and apoptosis to delineate its regulatory function. The investigation of mechanisms involving different models of hepatocyte proliferation contributes to our knowledge about serotonergic regulation of cell growth, apoptosis and carcinogenesis of liver. The study reveals that the alteration of the 5-HT1A and 5-HT2C receptor function and gene expression in the brain stem, cerebral cortex and hypothalamus play an important role in the sympathetic regulation of cell proliferation, neoplastic transformation and apoptosis. The functional balance between 5-HT1A and 5-HT2C receptor plays an important role in regulating hepatocyte proliferation, neoplastic transformation and hepatic apoptosis. The regulatory role of 5-HT1A and 5-HT2C receptor during neoplastic transformation and apoptosis could lead to possible therapeutic intervention in the treatment of cancers and have immense clinical importance.
Mohanan,Valiyaveettil; Finla, Chathu; Paulose, Cheramadathikudyil S(Department of Bio Technology, December 1, 2004)
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Abstract:
The purpose of this study was to investigate the role of central 5-HT2C receptor binding in rat model of pancreatic regeneration
using 60-70% pancreatectomy. The 5-HT and 5-HT2c receptor kinetics were studied in cerebral cortex and brain stem of sham
operated, 72 h pancreatectomised and 7 days pancreatectomised rats. Scatchard analysis with [3H] mesulergine in cerebral
cortex showed a significant decrease (p < 0.05) in maximal binding (B^,ax) without any change in Kd in 72 h pancreatectomised
rats compared with sham. The decreased Bmax reversed to sham level by 7 days after pancreatectomy. In brain stem , Scatchard
analysis showed a significant decrease (p < 0.01) in Bax with a significant increase (p < 0.01) in Kd. Competition analysis
in brain stem showed a shift in affinity towards a low affinity. These parameters were reversed to sham level by 7 days after
pancreatectomy. Thus the results suggest that 5-HT through the 5-HT2C receptor in the brain has a functional regulatory role in
the pancreatic regeneration. (Mol Cell Biochem 272: 165-170, 2005)
Epilepsy is a syndrome of episodic brain dysfunction characterized by recurrent unpredictable, spontaneous
seizures. Cerebellar dysfunction is a recognized complication of temporal lobe epilepsy and it is associated
with seizure generation, motor deficits and memory impairment. Serotonin is known to exert a modulatory
action on cerebellar function through 5HT2C receptors. 5-HT2C receptors are novel targets for developing anticonvulsant
drugs. In the present study, we investigated the changes in the 5-HT2C receptors binding and gene
expression in the cerebellum of control, epileptic and Bacopa monnieri treated epileptic rats. There was a
significant down regulation of the 5-HT content (pb0.001), 5-HT2C gene expression (pb0.001) and 5-HT2C
receptor binding (pb0.001) with an increased affinity (pb0.001). Carbamazepine and B. monnieri treatments
to epileptic rats reversed the down regulated 5-HT content (pb0.01), 5-HT2C receptor binding (pb0.001) and
gene expression (pb0.01) to near control level. Also, the Rotarod test confirms the motor dysfunction and
recovery by B. monnieri treatment. These data suggest the neuroprotective role of B. monnieri through the
upregulation of 5-HT2C receptor in epileptic rats. This has clinical significance in the management of epilepsy