Dopaminergic Regulation of Glucose-induced Insulin Secretion through Dopamine D2 Receptors in the Pancreatic Islets In Vitro

The stimulatory effect of dopamine through dopamine 1)2 receptor on glucose - induced insulin secretion was studied in the pancreatic islets in nitro. I)oparnilie signifieanlly stimula(ed insulin secretion at a concentration of 10 a N1 in the presence of high,glucose ( 20 nii1 ). ' fhe higher concentrations of dopamine (111 -1() 4) inhibited glucose- induced insulin secretion in the presence of both 4 mM1 and 20 m M glucose. Stimulatory and inhibitory effect of dopamine on glucose - induced insulin secretion was reverted by the addition of dopamine 1)2 receptor antagonists such as butaclamol and sulpiride . Norepinephrine (NE) at 111 4 11 concentration inhibited the dopamine uptake as well as its stimulatory effect at 11) - 8 IN1 concentration on glucose induced insulin secretion. Our results suggest that dopamine exerts a differential effect on glucose -induced insulin secretion through dopamine D2 receptor and it is essential for the regulation of glucose-induced insulin secretion by pancreatic islets.

Enhanced dopamine D2 receptor function in hypothalamus and corpus striatum: their role in liver, plasma and in vitro hepatocyte ALDH regulation in ethahol treated rats

Dopamine D2 receptors are involved in ethanol self- administration behavior and also suggested to mediate the onset and offset of ethanol drinking. In the present study, we investigated dopamine (DA) content and Dopamine D2 (DA D2) receptors in the hypothalamus and corpus striatum of ethanol treated rats and aldehyde dehydrogenase (ALDH) activity in the liver and plasma of ethanol treated rats and in vitro hepatocyte cultures. Hypothalamic and corpus striatal DA content decreased significantly (P\0.05, P\0.001 respectively) and homovanillic acid/ dopamine (HVA/DA) ratio increased significantly (P\0.001) in ethanol treated rats when compared to control. Scatchard analysis of [3H] YM-09151-2 binding to DA D2 receptors in hypothalamus showed a significant increase (P\0.001) in Bmax without any change in Kd in ethanol treated rats compared to control. The Kd of DA D2 receptors significantly decreased (P\0.05) in the corpus striatum of ethanol treated rats when compared to control. DA D2 receptor affinity in the hypothalamus and corpus striatum of control and ethanol treated rats fitted to a single site model with unity as Hill slope value. The in vitro studies on hepatocyte cultures showed that 10-5 M and 10-7 M DA can reverse the increased ALDH activity in 10% ethanol treated cells to near control level. Sulpiride, an antagonist of DA D2, reversed the effect of dopamine on 10% ethanol induced ALDH activity in hepatocytes. Our results showed a decreased dopamine concentration with enhanced DA D2 receptors in the hypothalamus and corpus striatum of ethanol treated rats. Also, increased ALDH was observed in the plasma and liver of ethanol treated rats and in vitro hepatocyte cultures with 10% ethanol as a compensatory mechanism for increased aldehyde production due to increased dopamine metabolism. A decrease in dopamine concentration in major brain regions is coupled with an increase in ALDH activity in liver and plasma, which contributes to the tendency for alcoholism. Since the administration of 10-5 M and 10-7 M DA can reverse the increased ALDH activity in ethanol treated cells to near control level, this has therapeutic application to correct ethanol addicts from addiction due to allergic reaction observed in aldehyde accumulation.

Superoxide dismutase functional regulation in neonatal hypoxia

Hypoxia is one of the major causes of damage to the fetal and neonatal brain and cardiac functions. in earlier studies we have reported the brain damage caused by hypoxia and resusciation with oxygen and epinephrine and have found that glucose treatment to hypoxic rats and hypoxic rats treated with oxygen shows a reversal of brain damage. during this study the findings may have clinical significance in the proper management of heart and brain functions.

Down-regulation of cerebellar 5-HT2C receptors in pilocarpine-induced epilepsy in rats: Therapeutic role of Bacopa monnieri extract

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

Decreased GABAA Receptors Functional Regulation 3 in the Cerebral Cortex and Brainstem of Hypoxic Neonatal Rats: 4 Effect of Glucose and Oxygen Supplementation

Hypoxia in neonates can lead to biochemical and molecular alterations mediated through changes in neurotransmitters resulting in permanent damage to brain. In this study, we evaluated the changes in the receptor status of GABAA in the cerebral cortex and brainstem of hypoxic neonatal rats and hypoxic rats supplemented with glucose and oxygen using binding assays and gene expression of GABAAa1 and GABAAc5. In the cerebral cortex and brainstem of hypoxic neonatal rats, a significant decrease in GABAA receptors was observed, which accounts for the respiratory inhibition. Hypoxic rats sup- plemented with glucose alone and with glucose and oxygen showed, respectively, a reversal of the GABAA receptors, andGABAAa1 and GABAAc5 gene expression to control. Glucose acts as an immediate energy source thereby reducing the ATP-depletion-induced increase in GABA and oxygenation, which helps in encountering anoxia. Resuscitation with oxygen alone was less effective in reversing the receptor alterations. Thus, the results of this study suggest that reduction in the GABAA receptors functional regulation during hypoxia plays an important role in mediating the brain damage. Glucose alone and glucose and oxygen supplementation to hypoxic neonatal rats helps in protecting the brain from severe hypoxic damage.

Dopamine D1 and D2 Receptor Gene Expression and cGMP, IP3 and Ca2+ Regulation in the Brain Regions of Hypoxic Neonatal Rats: Role of Glucose, Oxygen and Epinephrine Supplementation

Department of Biotechnology, Cochin University of Science and Technology

Glutamate Receptor Gene Expression: IP3, cAMP, cGMP Functional Regulation in Hypoglycaemic and Diabetic Rats

Department of Biotechnology, Cochin University of Science and Technology

5-HT2C and NMDA Receptors, IP3, cGMP and cAMP Functional Regulation in Pilocarpine Induced Temporal Lobe Epilepsy in Rats: Neuroprotective Role of Bacopa monnieri

Department of Biotechnology, Cochin University of Science and Technology

Elastic constant measurements of super ionic LiKSO4:Na single crystals

Elastic properties of sodium doped Lithium potassium sulphate, LiK0.9Na0.1SO4, crystal has been studied by ultrasonic Pulse Echo Overlap [PEO] technique and are reported for the first time. The controversy regarding the type of crystal found while growth is performed at 35 °C with equimolar fraction of Li2SO4H2O, K2SO4 and Na2SO4 has been resolved by studying the elastic properties. The importance of this crystal is that it exhibits pyroelectric, ferroelectric and electro optic properties. It is simultaneously ferroelastic and superionic. The elastic properties of LiK0.9Na0.1SO4 crystal are well studied by measuring ultrasonic velocity in the crystal in certain specified crystallographic directions and evaluating the elastic stiffness constants, compliance constants and Poisson’s ratios. The anisotropy in the elastic properties of the crystal are well explained by the pictorial representation of the surface plots of phase velocity, slowness and linear compressibility in a-b and a-c planes.

DOPAMINE D2 RECEPTOR FUNCTIONAL REGULATION : cAMP AND IP3 ROLE IN PANCREATIC REGENERATION

The present study deals with the differential regulation of Dopamine content in pancreas and functional regulation of Dopamine D2 receptor in brain regions such as hypothalamus, brain stem, cerebral cortex and corpus striatum play an important role during pancreatic islets cell proliferation and insulin secretion. Though may reports are there implicating the functional interaction between DA receptor and pancreatic islets cell insulin secretion, the involvement of specific DA D2 receptors and changes in second messenger system during insulin secretion and pancreatic islets cell proliferation were not given emphasis. Down regulation of DA content in brain regions and pancreatic islets were observed during pancreatic regeneration. Up regulation of DA content in plasma and adrenals down regulated sympathetic activity in pancreas which cause an increase in insulin secretion and pancreatic islets cell proliferation during pancreatic regeneration. There was a differential regulation of DA D2 receptor in brain regions. The pancreatic islets DA D2 receptors were lip regulated during pancreatic regeneration. DA D2 receptor activation at specific concentration has accounted for increased pancreatic islets cell proliferation. In vitro experiments have proved the differential regulation of DA on insulin synthesis and pancreatic islets cell proliferation. Inhibitory effect of DA on cAMP and stimulatory effect of DA on IP3 through DA D2 receptors were observed in in vitro cell culture system. These effects are correlating with the DA, cAMP and IP3 content during pancreatic regeneration and islets cell proliferation. Up regulation of intracellular Ca2+ was also observed at 10-8 M DA, a specific concentration of DA which showed maximum increase of IP3 content in pancreatic islets through DA D2 receptor activation in in vitro culture. These in vitro data was highly correlating with the changes in DA, cAMP and IP3 content in pancreas during pancreatic regeneration and insulin secretion. Thus we conclude that there is a differential functional regulation of DA and DA D2 receptors in brain and pancreas during pancreatic regeneration. In vitro studies confirmed a concentration depend functional regulation of DA through DA D2 receptors on pancreatic islets cell proliferation and insulin secretion mediated through increased cAMP, IP3 and intracellular Ca2+ level. This will have immense clinical significance in the management in diabetes mellitus.

GABA, serotonin, muscarinic receptors - their second messengers and transcription factors functional regulation in the brain regions of hypoxic neonatal rats: Resuscitation with glucose, oxygen and epinephrine

The present study was designed to investigate the protective effect of glucose, oxygen and epinephrine resuscitation on impairment in the functional role of GABAergic, serotonergic, muscarinic receptors, PLC, BAX, SOD, CAT and GPx expression in the brain regions of hypoxia induced neonatal rats. Also, the role of hormones - Triiodothyronine (T3) and insulin, second messengers – cAMP, cGMP and IP3 and transcription factors – HIF and CREB in the regulation of neonatal hypoxia and its resuscitation methods were studied. Behavioural studies were conducted to evaluate the motor function and cognitive deficit in one month old control and experimental rats. The efficient and timely supplementation of glucose plays a crucial role in correcting the molecular changes due to hypoxia, oxygen and epinephrine. The sequence of glucose, epinephrine and oxygen administration at the molecular level is an important aspect of the study. The additive neuronal damage effect due to oxygen and epinephrine treatment is another important observation. The corrective measures by initial supply of glucose to hypoxic neonatal rats showed from the molecular study when brought to practice will lead to healthy intellectual capacity during the later developmental stages, which has immense clinical significance in neonatal care.

Biochemical Effects of Anionic, Cationic and Non Ionic Surfactants on a Tropical Teleost Oreochromis Mossambicus(Peters) and a Marine Cyanobacterium Synechocystis Salina Wislouch

The present work is a base line attempt to investigate and assess the toxicities of three surfactants viz. anionic sodium dodecyl sulfate (SDS), non ionic Triton X-1OO (TX-IOO) and cationic cetyl trimethyl ammonium bromide (CTAB). These compounds represent simple members of the often neglected group of aquatic pollutants i.e. the anionic alkyl sulfates, non ionics and the cationics. These compounds are widely used In plastic industry, pesticide/herbicide formulations, detergents, oil spill dispersants, molluscicides etc. The test organisms selected for the present study are the cyanobacterium Synechocystis salina Wislouch representing a primary producer in the marine environment and a fresh water adapted euryhaline teleost Oreochromis mossambicus (peters) at the consumer level of the ecological pyramid. The fish species, though not indigenous to our country, is now found ubiquitously in fresh water systems and estuaries. Also it is highly resistant to pollutants and has been suggested as an indicator of pollution in tropical region .