Search PubMed⌕ Search

Biomedical subjects

S C Pandey

Publications and source records attributed to S C Pandey.

At least 37 records · Page 2Linked to original sources
PubMed1997

Protein kinase C in the postmortem brain of teenage suicide victims.

Increased serotonin2A (5-HT2A) receptors have been reported in the postmortem brain of suicide victims. To examine if this increase is associated with the dysregulation of postreceptor sites in the signaling cascade, we determined [3H]phorbol dibutyrate (PDBU) binding to protein kinase C (PKC) in postmortem brain samples (Brodmann's areas 8 and 9) obtained from teenage suicide victims and control subjects. [3H]PDBU binding to PKC was determined in membranal and cytosolic fractions. We observed that Bmax of [3H]PDBU binding sites was significantly decreased in both membranal and cytosolic fractions in brain samples from Brodmann's areas 8-9 compared to matched controls. These results thus suggest that PKC may play a role in the pathophysiology of suicidal behavior.

Adolescent↗
PubMed1996

Effects of chronic nicotine treatment on the expression of phospholipase C isozymes and the alpha subunit of Gq/11 protein in the rat brain.

The effect of chronic nicotine treatment on postreceptor sites of the phosphoinositide (PI) signaling system (i.e. phospholipase C (PLC) isozymes, Gq/11 protein) in the rat cortex was investigated. The expression of PLC isozymes (beta 1, gamma 1, and delta 1) and the alpha subunit of Gq/11 protein in the cortices of rats treated with saline or nicotine was determined by the Western blot technique using specific monoclonal antibodies. It was observed that chronic nicotine treatment (10 days) significantly increased the immunolabeling of the total PLC-beta 1, which was due to an increase in the immunolabeling of both the membranal and the cytosolic PLC-beta 1 isozyme in the rat cortex. On the other hand, the immunolabeling of total, membranal, and cytosolic PLC-delta 1 and -gamma 1 isozymes in the rat cortex was not significantly altered by chronic nicotine treatment. In addition, Western blot analysis also demonstrated that chronic nicotine treatment has no significant effect on the immunolabeling of the alpha subunit of Gq/11 protein in the rat cortex. Thus, these findings suggest that an increase in the expression of the PLC-beta 1 isozyme may be involved in the neuroadaptational mechanisms associated with tobacco addiction.

Animals↗
PubMed1996

Modulation of serotonin2A/2C receptors and these receptor-linked phosphoinositide system by ethanol.

Studies related to 5-HT2A/2C receptors and these receptor-linked phosphoinositide (PI) system in the rat brain during chronic ethanol treatment and withdrawal are discussed. Chronic ethanol treatment (60 days) has no effect on 5-HT2A/2C receptors in the cortex and the hippocampus but significantly decreased 5-HT-stimulated PI hydrolysis in the rat cortex. On the other hand, chronic ethanol treatment (60 days) significantly increased 5-HT2C receptors and 5-HT-stimulated PI hydrolysis in the rat choroid plexus. Ethanol withdrawal (24 h) after chronic ethanol consumption (15 days) results in the down-regulation of 5-HT2A receptors and in a decrease in 5-HT-stimulated PI hydrolysis in the rat cortex. Taken together, these results, along with other reports in the literature, suggest that 5-HT2A/2C receptors or their function are altered during chronic ethanol consumption and withdrawal. Further studies are needed to explore the role of 5-HT2A/2C receptors and the PI signal transduction system in the development of ethanol withdrawal symptoms after chronic ethanol consumption.

Alcoholism↗
PubMed1996

Alterations in serotonin1B (5HT1B) receptor subtypes in the brain of ethanol-treated rats.

The effects of acute or chronic ethanol treatment and of withdrawal (24 h) after chronic ethanol treatment on 5HT1B receptor subtypes in different regions of the rat brain were investigated. Male Sprague-Dawley rats were fed the ethanol (9% v/v)-containing Lieber-DeCarli liquid diet or the control liquid diet for 1 day in the acute study and for 15 days in the chronic study. The ethanol-withdrawn group received the Lieber-DeCarli control liquid diet instead of the ethanol diet on the 15th night. Ethanol-withdrawn rats after 15 days of ethanol treatment were rated for withdrawal symptoms (e.g. hyperactivity, piloerection, squealing, and enhanced startle reflex) and were found to exhibit such symptoms after 24 h of ethanol withdrawal. The rats were decapitated, and cortices, cerebelli, striata, and hippocampi were separated for measurement of 5HT1B receptors by receptor binding techniques using 125I-cyanopindolol (CYP) as the ligand. It was observed that acute ethanol treatment had no significant effect on the maximum number of binding sites (Bmax) or the apparent dissociation constant (KD) of 5HT1B receptor binding sites in the various brain regions. On the other hand, chronic ethanol treatment produced a significant increase in Bmax of 125I-CYP binding to 5HT1B receptors in the rat cortex and hippocampus, which remained increased after 24 h of ethanol withdrawal. In contrast, in the striatum and the cerebellum of chronic ethanol-treated and withdrawn rats, the 5HT1B binding parameters (Bmax and KD) were unchanged. These results suggest the possible involvement of cortical and hippocampal 5HT1B receptors in ethanol dependence.

Animals↗
PubMed1996

Acute and chronic ethanol consumption effects on the immunolabeling of Gq/11 alpha subunit protein and phospholipase C isozymes in the rat brain.

The goal of this investigation was to examine whether postreceptor sites [Gq/11 protein and phospholipase C (PLC) isozymes] of the phosphoinositide signal transduction system are involved in neuroadaptational mechanisms in the brain during chronic ethanol consumption. It was observed that acute ethanol treatment has no effect on the immunolabeling of PLC-beta 1, -gamma 1, and -delta 1 and the alpha subunit of Gq/11 protein in the rat cortex as determined by western blotting using specific monoclonal antibodies. On the other hand, chronic ethanol consumption (15 days) resulted in a significant decrease in the immunolabeling of PLC-beta 1, whereas under identical conditions, the immunolabeling of PLC-gamma 1 and -delta 1 isozymes was not significantly altered. The decreased immunolabeling of PLC-beta 1 during chronic ethanol consumption was not altered by 24 h of withdrawal after 15 days of ethanol consumption. The immunolabeling of the alpha subunit of Gq/11 protein was significantly decreased after 15 days of ethanol consumption but had returned to normal levels after 24 h of ethanol withdrawal. Also, chronic ethanol treatment resulted in a significant decrease in phosphatidylinositol 4,5-bisphosphate-specific PLC activity, which remained the same after 24 h of ethanol withdrawal. These results suggest that decreased PLC activity during ethanol consumption and its withdrawal may be due to decreased protein levels of the Gq/11 protein-coupled PLC-beta 1 isozyme but not the PLC-gamma 1 or -delta 1 isozyme in the rat cortex. It is possible that changes in the protein levels of the Gq/11 protein-coupled PLC-beta 1 isozyme and in PLC activity in the brain may be involved in the cellular adaptation to chronic ethanol exposure.

Alcohol Drinking↗
PubMed1996

Serotonin2C receptors and serotonin2C receptor-mediated phosphoinositide hydrolysis in the brain of alcohol-preferring and alcohol-nonpreferring rats.

To examine the role of serotonin2C (5HT2C) receptors in alcohol drinking behavior, the binding indices of 5HT2C receptors were determined in various brain regions of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. 5HT2C receptor-mediated phosphoinositide hydrolysis in the choroid plexus of P and NP rats was also determined. It was observed that the densities of 5HT2C receptors are significantly higher in the hippocampus, the amygdala, and the choroid plexus, but not in the cortex of P rats compared with NP rats. The Kd values of [3H]mesulergine binding to 5HT2C receptors were not different in these brain regions of P rats compared with NP rats. It was also observed that 5HT-stimulated [3H]inositol 1-phosphate formation was significantly higher in the choroid plexus of P rats compared with NP rats. The results of this study indicate that the numbers of 5HT2C receptors are higher in the hippocampus, the amygdala, and the choroid plexus, and that 5HT2C receptor-mediated phosphoinositide hydrolysis is more elevated in the choroid plexus of P rats compared with NP rats. Thus, it seems from these results that increased 5HT2C receptors may be involved in the genetic vulnerability to alcohol drinking behavior.

Alcohol Drinking↗
PubMed1995

Platelet serotonin-2A receptors: a potential biological marker for suicidal behavior.

OBJECTIVE: Abnormalities in the serotonergic system have been implicated in suicidal behavior. Higher numbers of serotonin-2 (5-HT2) receptors have been reported in the post-mortem brain of suicide victims. In order to further examine the role of 5-HT2A receptors in suicidal behavior, the authors studied 5-HT2A receptors in platelets of suicidal and nonsuicidal patients as well as normal comparison subjects. METHOD: 5-HT2A receptor levels were determined by using [125I]LSD as a radioligand in platelets obtained from hospitalized psychiatric patients (N = 131) and nonhospitalized normal comparison subjects (N = 40) during a drug-free baseline period. Patients were diagnosed according to DSM-III-R criteria, and suicidal behavior was identified by using the Hamilton Depression Rating Scale. RESULTS: The mean maximum number of binding sites (Bmax) of platelet 5-HT2A receptors for all suicidal patients was significantly higher than for nonsuicidal patients or normal comparison subjects. This significant difference remained when subgroups of suicidal patients with depression, schizophrenia, schizoaffective disorder, or bipolar illness were compared to the other two subject groups. The higher number of platelet 5-HT2A receptors in suicidal patients was independent of diagnosis. While there was no significant difference in Bmax between patients with serious suicidal ideation and those who made suicidal attempts, both groups had significantly higher Bmax than normal comparison subjects. CONCLUSIONS: The observed higher number of platelet 5-HT2A receptors in suicidal patients is independent of diagnosis and appears to be associated with both the brain and the platelets of suicidal patients. These results thus suggest the potential usefulness of platelet 5-HT2A receptors as a biological marker for identifying suicide-prone patients.

Adult↗
PubMed1995

Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates.

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.

Alcoholism↗
PubMed1994

Peripheral benzodiazepine receptors are decreased during cocaine withdrawal in humans.

In the present study, homovanillic acid in plasma (pHVA) and benzodiazepine receptors (3H-PK11195 binding) in neutrophil membranes were determined in blood obtained from cocaine-dependent (DSM-III-R) adult male inpatients at baseline-(within 72 hr of last cocaine use) and after 3 weeks of cocaine abstinence, and normal controls. The mean (+/- SEM) pHVA at baseline (10.3 ng/ml +/- 1.1) was similar to normals and did not change after 3 weeks of cocaine abstinence. Similarly, the binding indices of benzodiazepine receptors in cocaine-dependent subjects as a group were not significantly different than in normal controls. In 10 cocaine-dependent subjects, however, where both blood samples were available, the number of 3H-PK11195 binding sites was significantly (p < 0.05) decreased after 3 weeks of cocaine abstinence (mean +/- sem: Bmax = 6371 +/- 657 fmol/mg protein) compared with baseline (Bmax = 7553 +/- 925 fmol/mg protein), although there were no differences in the binding affinity (mean +/- sem: KD = 8.6 +/- 1.2 nmol/L after 3 weeks of abstinence compared with 8.1 +/- 1.0 nmol/L at baseline). These preliminary results suggest that peripheral benzodiazepine receptors may play an important role in the pathophysiology of cocaine withdrawal in cocaine-dependent human subjects.

Adult↗
PubMed1994

The effects of in vivo cocaine on norepinephrine-stimulated phosphoinositide hydrolysis in rat brain.

We examined the effects of a cocaine challenge on behavioral stimulation and NE-stimulated [3H]inositol-1-phosphate (IP1) formation in rat cerebral cortex after single (high dose) or repeated (low dose) cocaine administration. As previously reported, single high dose (40 mg/kg, IP) and repeated low dose (10 mg/kg, 8 IP injections) administrations of cocaine resulted in behavioral sensitization to a challenge injection of cocaine (10 mg/kg). In saline-pretreated animals, the acute cocaine challenge significantly potentiated the NE-stimulated [3H]IP1 formation as compared with the saline challenge, while in cocaine-pretreated animals, NE-stimulated phosphoinositide (PI) turnover was not significantly altered. These results suggest that although some of the acute effects of cocaine may be mediated by enhanced alpha 1-adrenergic receptor-linked PI hydrolysis, behavioral sensitization does not involve the alpha 1-adrenergic receptor-linked PI signal transduction system.

Animals↗
PubMed1993

Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus.

The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5-HT1C receptors without causing a significant change in affinity (KD) of [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT1C receptors in brain. These results also suggest that 5-HT1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.

Animals↗
PubMed1993

Repeated cocaine administration does not affect 5-HT receptor subtypes (5-HT1A, 5-HT2) in several rat brain regions.

In order to examine whether cocaine-induced behavioral sensitization is modulated by changes in serotonin receptor subtypes, we measured the binding of [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) to 5-HT1A receptors and of [3H]-ketanserin to 5-HT2 receptors in various brain regions of cocaine-treated and saline-treated (control) rats. As previously reported, repeated administration of cocaine resulted in behavioral sensitization. Stereotypic scores with the cocaine challenge were significantly (P < 0.05) higher in cocaine-pretreated animals than in the saline-pretreated group. Neither acute nor chronic cocaine administration significantly altered the number (Bmax) or the affinity (KD) of either [3H]8-OH-DPAT or [3H]ketanserin binding sites in any of the brain regions examined. These results suggest that the enhanced functional sensitivity of 5-HT1A or 5-HT2 receptor subtypes seen with cocaine may be associated with alterations in processes distal to receptors rather than changes in the number or the affinity of the receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1993

Platelet serotonin-2 receptors in obsessive-compulsive disorder.

To examine the role of serotonin-2 (5-HT2) receptors in obsessive-compulsive disorder (OCD), we studied 5-HT2 receptors in platelets obtained from patients with OCD (n = 20) during a drug free baseline period, as well as in normal control subjects (n = 25). The maximum number of binding sites (Bmax) and the apparent dissociation constant (Kd) of 5-HT2 receptors were determined by receptor binding techniques using 125I-lysergic acid diethylamide (LSD) as radioligand. We observed that the mean Bmax of 125I-LSD binding in platelets of patients with OCD was not significantly different when compared with normal control subjects. There was also no significant difference in Kd values between patients with OCD and normal control subjects. To examine whether the baseline 5-HT2 receptors are related to the severity of illness, we determined the relationships of the baseline Bmax and Kd with baseline scores of the Hamilton Depression Rating Scale (HDRS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the National Institute of Mental Health (NIMH) Obsessive-Compulsive scale (GOCS). We found no significant correlation between baseline Bmax and Kd with the baseline HDRS, Y-BOCS, or NIMH-GOCS scores. Our results do not indicate abnormal 5-HT2 receptors in platelets of patients with OCD.

Adult↗
PubMed1993

Platelet serotonin-2 receptors in schizophrenia: effects of illness and neuroleptic treatment.

To examine the role of serotonin2 (5-hydroxytryptamine2, 5-HT2) receptors in schizophrenia, we determined the binding indices of 5-HT2 receptors using 125I-lysergic acid diethylamide (LSD) as the radioligand in platelets obtained from 40 normal control subjects and 42 drug-free schizophrenic patients. We also examined the effect of neuroleptic drug treatment on the binding parameters (Bmax and Kd) of 5-HT2 receptors in platelets of schizophrenic patients. We observed that the Bmax of 125I-LSD binding in platelets of schizophrenic patients was significantly higher than in platelets of normal subjects. There was no significant difference, however, between the Kd of 125I-LSD binding in platelets of schizophrenic patients and normal control subjects. Furthermore, we found no correlation between Brief Psychiatric Rating Scale scores and either Bmax or Kd of 125I-LSD binding at the end of the drug washout period. We also observed that neither treatment with haloperidol nor treatment with thiothixine caused significant changes in Bmax and Kd of 125I-LSD binding in platelets of schizophrenic patients. However, both fluphenazine and trifluoperazine did significantly increase the Bmax of 125I-LSD binding without any significant change in the Kd values in platelets of schizophrenic patients. Our results thus suggest that platelet 5-HT2 receptors are increased in schizophrenia and that chronic treatment with fluphenazine and trifluoperazine, but not haloperidol or thiothixine, further increases the 5-HT2 receptor binding sites in platelets of schizophrenic patients.

Adult↗
PubMed1992

Effect of electroconvulsive shock on 5-HT2 and alpha 1-adrenoceptors and phosphoinositide signalling system in rat brain.

We studied the effect of repeated administration of electroconvulsive shock (ECS) on alpha 1-adrenoceptor subtype (alpha 1A and alpha 1B) and 5-HT2 (serotonin-2) receptors and receptor-mediated phosphoinositide (PI) hydrolysis in rat cerebral cortex. We observed that repeated administration with ECS significantly increased the density of 5-HT2 receptors, as labeled by [3H]ketanserin, as well as 5-HT-stimulated [3H]inositol-1-phosphate ([3H]IP1) in rat cerebral cortex. We also observed that repeated ECS administration caused a significant increase in the number of alpha 1-adrenoceptors and the alpha 1B-adrenoceptor subtype as measured by (+/-)-beta-([125I]iodo-4-hydroxyphenyl)-ethyl-aminomethyl-tetralone binding. However, it had no significant effects on norepinephrine (NE)-stimulated [3H]IP1 formation or alpha 1A-adrenoceptor subtype. These results thus suggest that up-regulation of 5-HT2 receptors after administration with ECS is associated with increased 5-HT-stimulated [3H]IP1 formation. The lack of effects on NE-stimulated PI turnover in ECS treated rats may be due to its lack of effect on the alpha 1A-adrenoceptor subtype.

Animals↗
PubMed1992

Effect of ethanol administration and withdrawal on serotonin receptor subtypes and receptor-mediated phosphoinositide hydrolysis in rat brain.

The effect of short-term (15 days) and long-term (60 days) ethanol treatment and withdrawal on agonist-stimulated phosphoinositide (Pl) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and alpha 1-adrenergic receptors were studied in rat cerebral cortex. Short-term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)-stimulated [3H]-inositol-1-phosphate ([3H]-IP1) formation and 5-HT2 receptors as measured by 125I-lysergic acid diethylamide (125I-LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I-LSD binding without significant change in KD, as well as a decrease in 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. 5HT1A and alpha 1-adrenergic receptors were determined by using [3H]-8-hydroxy-2-(di-N-propylamino)tetralin and [3H]-prazosin as radioligand, respectively. We also observed that long-term ethanol treatment had no significant effect on Bmax and KD of 5HT2, 5HT1A, and alpha 1-adrenergic receptors, as well as NE and A23187-stimulated [3H]-IP1 formation, but significantly decreased the 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. It is possible that a decrease in 5HT-induced PI turnover after long-term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT-induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.

8-Hydroxy-2-(di-n-propylamino)tetralin↗