PubMed Health⌕ Search

Biomedical subjects

T K Chatterjee

Publications and source records attributed to T K Chatterjee.

At least 37 records · Page 2Linked to original sources
PubMed1991

Characterization and regulation of high affinity calcitonin gene-related peptide receptors in cultured neonatal rat cardiac myocytes.

Previous studies have shown that stimulation of cultured beating cardiac myocytes with calcitonin gene-related peptide (CGRP) produces increased beating frequency, increased cellular cAMP concentration, and a homologous desensitization of the cAMP-elevating action of CGRP. In the present study, the characteristics and regulation of [125I]CGRP binding sites in cultured cardiac myocytes were investigated. Binding of [125I] CGRP to membranes prepared from these cells was selective, saturable, and of high affinity. Scatchard transformation of the saturation isotherm generated a linear plot suggesting the existence of a homogeneous population of binding sites with an equilibrium binding constant of 41 +/- 7 pM and maximum binding capacity of 31 +/- 5 fmol/mg protein. Binding of [125I]CGRP to membranes was inhibited completely by guanosine 5'-(3-O-thio)triphosphate (250 microM), suggesting association of the binding sites with a G protein. Consistent with the saturation binding data, association kinetic studies indicated that [125I]CGRP associated with a single population of binding sites. Dissociation kinetic data, in contrast, indicated that [125I]CGRP dissociated from two affinity component sites on membranes, suggesting the existence of multiple affinity states of the G protein-coupled forms of the CGRP receptor. Nonequilibrium dissociation kinetic experiments revealed a time-dependent conversion of [125I] CGRP binding sites from a fast- to a slow-dissociating state. Desensitization of cells to CGRP by prior exposure to CGRP (10 nM) for 5 min reduced the maximal cAMP response of cells to further CGRP challenge and the number of [125I]CGRP binding sites in membranes prepared from these cells approximately 90% and 80%, respectively. These results demonstrate the existence of high affinity CGRP receptors in cardiac myocytes which appear coupled to G proteins and which undergo ligand-induced affinity alterations and desensitization-induced loss of receptor activity. The present findings also suggest the existence of multiple affinity states of the CGRP:receptor:G protein ternary complex.

Animals↗
PubMed1991

Multiple affinity forms of the calcitonin gene-related peptide receptor in rat cerebellum.

Binding of 125I-calcitonin gene-related peptide (125I-CGRP) to rat cerebellum membranes and the sensitivity to guanine nucleotides of binding were investigated. Cerebellum binding sites labeled by 125I-CGRP appear to be highly specific, inasmuch as CGRP inhibited binding with an IC50 of 100 pM but other peptides were inactive or much less active in displacing 125I-CGRP from these sites. 125I-CGRP binding sites in cerebellum membranes were saturable and of high affinity. Scatchard analysis of the saturation binding data revealed a homogeneous population of binding sites, with a KD of 224 +/- 28 pM and Bmax of 131 +/- 15 fmol/mg of protein. In the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) (100 microM), a single population of binding sites, with a KD of 464 +/- 77 pM and Bmax of 100 +/- 14 fmol/mg of protein, was observed. The kinetics of association of 125I-CGRP with cerebellum membranes were monophasic at all ligand concentrations tested. However, the observed association rate constant (kobs) was not dependent on [125I-CGRP] in a linear fashion in either the absence or the presence of GTP gamma S (100 microM). The kinetics of dissociation of 125I-CGRP from cerebellum membranes were multiexponential, with fast and slow dissociating components having rate constants of 0.34 +/- 0.01 and 0.025 +/- 0.001 min-1, respectively. The fast dissociating component represented 60 +/- 2% of the total specific binding sites. Dissociation of 125I-CGRP from cerebellum sites was much faster in the presence of GTP gamma S (100 microM) but still exhibited dissociation from two affinity components. The rate constants for these components of dissociation were 0.67 +/- 0.03 and 0.077 +/- 0.007 min-1, with the faster dissociating component representing 66 +/- 1% of the total specific binding sites. These findings provide the first evidence that CGRP receptors exist in multiple affinity states and that cerebellum CGRP receptors are regulated by guanine nucleotides. Our results also suggest the existence of two affinity states of the CGRP-receptor-guanine nucleotide-binding protein ternary complex.

Animals↗
PubMed1990

Duodenal tuberculosis: a review of the clinicopathologic features and management of twelve cases.

A retrospective analysis of twelve cases of duodenal tuberculosis is presented herein. The average age of the patients was 31.4 years with a male to female ratio of 2:1. The presenting complaints were duodenal obstruction in six patients and subacute intestinal obstruction in three. None of the patients had associated pulmonary tuberculosis. Eight patients had isolated duodenal tuberculosis, two of whom were successfully treated with antitubercular drugs. In four patients, the diagnosis was established at laparotomy by the presence of tubercles over the duodenum. Five patients required a bypass procedure for obstruction caused by the duodenal tuberculosis and one patient was operated on for uncontrollable bleeding from a tubercular duodenal ulcer. All patients remained symptom free after treatment, whether medical or surgical. Thus, in areas where tuberculosis is endemic, even in the absence of pulmonary tuberculosis, duodenal tuberculosis should be suspected in patients with upper gastrointestinal obstruction or in patients with peptic ulcer like symptoms not responding to medical therapy.

Adult↗
PubMed1990

Ca2(+)-dependent, ATP-induced conversion of the [3H]hemicholinium-3 binding sites from high- to low-affinity states in rat striatum: effect of protein kinase inhibitors on this affinity conversion and synaptosomal choline transport.

Tritium-labeled hemicholinium-3 ([3H]HC-3) was used to characterize the sodium-dependent high-affinity choline carrier sites in rat striatal preparations. In an earlier study, we had shown that [3H]HC-3 labels choline carrier sites with high and low affinities and had suggested that the low-affinity sites represent "functional" carrier sites. The objective of the present study was to examine the mechanisms involved in the regulation of the two affinity states of [3H]HC-3 binding. Here, we demonstrate that these two affinity states are totally interconvertible; addition of 0.1 mM ATP in the binding assay medium quantitatively converted all the binding sites to the low-affinity state, whereas addition of 1 mM beta,gamma-methylene 5'-ATP quantitatively converted all the binding sites to the high-affinity state. Preincubation of the tissue (for 15 min at 37 degrees C) before the binding assay also converted the binding sites to the high-affinity state, whereas supplementation of the assay medium with ATP (0.5 mM) again induced expression of the low-affinity state of the binding sites. This effect of ATP was found to be selective for this nucleotide. Neither ADP (1 mM) nor cyclic AMP could mimic such an effect. Other nucleotide triphosphates--CTP (0.5 mM) and GTP (0.5 mM)--also could not substitute for ATP. GTP, however, caused nearly a 35% reduction in the number of binding sites, accompanying a loss of the low-affinity component of binding. This effect of GTP was also shared by 5'-guanylylimidodiphosphate but not by GDP or cyclic GMP. This ATP-dependent low-affinity conversion of [3H]HC-3 binding sites requires divalent metal ions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Methylpiperidine analog of hemicholinium-3: a selective, high affinity non-competitive inhibitor of sodium dependent choline uptake system.

The potency of hemicholinium-3 (HC-3) and its analogs to inhibit sodium dependent high affinity choline uptake were evaluated in rat striatal synaptosomal preparation. Hemicholinium-3 inhibited sodium dependent high affinity choline uptake (IC50 = 18 nM) while the half molecule of HC-3, HC-15, was inactive. The order of potency for choline uptake inhibition of piperidine substituted HC-3 molecule was as follows: 4-methylpiperidine (A-5 and CA-5) much greater than HC-3 much greater than unsubstituted piperidines (CA-1 and A-1) much greater than 2- or 3-methylpiperidine (A-2 and A-3) and 4-hydroxypiperidine (A-7). The tertiary amine derivative of 4-methylpiperidine substituted HC-3 (A-4) was nearly 10-fold less potent than its corresponding quaternary derivative (A-5). Choline uptake was inhibited competitively by HC-3 and non-competitively by A-5. The inhibition of choline uptake by A-5 was readily reversible by washing. A-5 did not inhibit the uptake of dopamine and gamma-aminobutyric acid. These findings suggest that the N-methyl,4-methylpiperidine analog of HC-3 (A-5) is the most potent of all known inhibitors of sodium dependent high affinity choline uptake and that the inhibition of choline uptake by this compound is mediated through a mechanism distinct from a simple competitive one.

Animals↗
PubMed1988

(R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist.

Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

Animals↗
PubMed1988

Interaction of [3H]spiperone with rat striatal dopamine D-2 receptors: kinetic evidence for antagonist-induced formation of ternary complex.

The characteristics of [3H]spiperone interactions with rat striatal dopamine D-2 receptor were investigated. Although the association of [3H]spiperone occurred monoexponentially, the pseudo-first order rate constant of association showed a hyperbolic dependence on ligand concentration. The data were therefore analyzed with the assumption of a two-step binding reaction leading to ligand-induced receptor isomerization. For the first equilibrium, the dissociation constant (KD) was 1.2 nM, while for the second equilibrium, the association and the dissociation rate constants were 71.6 X 10(-3) sec-1 and 0.9 X 10(-3) sec-1, respectively. The dissociation rate constant of the overall binding reaction, as determined by inducing the dissociation of [3H]spiperone from its binding sites by 1 microM (+)-butaclamol, was 0.92 X 10(-3) sec-1. However, the kinetically derived KD (15 pM) of the binding reaction differed significantly from the KD (218 pM) obtained from equilibrium binding experiments. This inconsistency between the two KD values appeared to have arisen from using different receptor concentrations in deriving kinetic and equilibrium data. The KD of the equilibrium binding reaction indeed showed significant variation with the receptor concentrations in an inverse way, implicating the involvement of a third component in the two-step binding reaction to form a high affinity ternary complex rather than a simple ligand induced receptor isomerization. Pretreatment of the membrane with 0.1 mM guanosine 5'-imidodiphosphate [Gpp(NH)p] reduced the affinity of the equilibrium binding reaction to a value (KD = 1.2 nM) which corresponded to the kinetically derived KD of the first step of the binding reaction, indicating the involvement of a guanine nucleotide-binding protein or G protein in inducing the formation of the high affinity ternary complex. The affinity of the binding reaction in Gpp(NH)p-pretreated membranes, however, increased with the duration of incubation, indicating that the ligand receptor complex still can couple with the G protein even in the presence of Gpp(NH)p. Pretreatment of the membrane with pertussis toxin irreversibly decreased the affinity of the binding reaction without significantly affecting the total number of binding sites, implying the involvement of the Gi subclass of G protein in the interaction of [3H]spiperone with D-2 receptors. Inhibition of the [3H]spiperone binding by a dopamine receptor agonist, bromocriptine, also yielded a monophasic dose response curve both in the presence and in the absence of Gpp(NH)p.(ABSTRACT TRUNCATED AT 400 WORDS)

Algorithms↗
PubMed1987

Characteristics of [3H]hemicholinium-3 binding to rat striatal membranes: evidence for negative cooperative site-site interactions.

The characteristics of [3H]hemicholinium-3 ([3H]HC-3) interactions with rat striatal membranes were investigated. Under the described assay conditions, [3H]-HC-3 binds with a saturable population of membrane binding sites having the following regional distribution: striatum much greater than hippocampus greater than or equal to cerebral cortex greater than cerebellum. The specific binding of [3H]HC-3 showed an obligatory requirement for NaCl; other halide salts of sodium or KCl failed to substitute for NaCl. The Scatchard transformation of saturation isotherm data generated a curvilinear plot with high- and low-affinity components of binding. The dissociation of [3H]HC-3 at infinite dilution was also multiexponential. The dissociation could, however, be accelerated if unlabeled HC-3 was included in the diluting buffer, and this increase in dissociation appeared to be dependent on the concentrations of unlabeled HC-3 used, with the maximal increase demonstrable at 100 nM. The dissociation was also dependent on the fractional saturation of binding sites with labeled HC-3, such that, at higher fractional saturation of binding sites, the overall dissociation was faster and the difference in the dissociation observed between "dilution only" and "dilution + unlabeled HC-3" was reduced. This occupancy-dependent change in dissociation could also be influenced by temperature and pH. Based on the results of these kinetic studies, the steady-state [3H]HC-3 binding data were analyzed for a homogeneous population of binding sites undergoing site-site interactions of the negative cooperative type. Such an analysis yielded a KD of 9.3 nM for the high-affinity state and a KD of 22.8 nM for the low-affinity state of binding sites, with a Bmax of 434 fmol/mg of protein. Competitive binding studies showed that unlabeled HC-3 was most potent in displacing [3H]HC-3, followed by choline. Other drugs known to have little influence on the synaptosomal sodium-dependent high-affinity choline uptake system (SDHACU) had no significant effect on [3H]HC-3 binding sites. Similarities in ionic dependencies, regional distributions, and pharmacological selectivities of [3H]HC-3 binding with synaptosomal SDHACU suggest that [3H]HC-3 selectively labels SDHACU sites located on presynaptic cholinergic neurons in rat CNS. We suggest that the two affinity states of [3H]HC-3 binding sites represent the different "functional" states of the SDHACU system. The binding of HC-3 (or choline) with the high-affinity state of the binding sites induces negative cooperative site-site interactions among the binding sites, resulting in the formation of a low-affinity binding state.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Chemotherapy in buccal mucosa cancer.

Twenty-five patients with previously untreated squamous cell carcinoma of the buccal mucosa were treated by two chemotherapeutic regimens. The first regimen consisted of administration of methotrexate (50 mg) intravenously at weekly intervals for 3 weeks. The second regimen consisted of bleomycin and methotrexate (BLM-MTX): Bleomycin 30 mg was given intravenously twice weekly and methotrexate 25 mg intravenously twice weekly for 2 1/2 and 2 weeks, respectively. Twenty-two of 25 cases were subjected to radical surgery following chemotherapy. When the two groups are compared, the number of cases responding to chemotherapy is about equal (70% and 73.4%). The observations suggest that the buccal cancers are highly sensitive to initial treatment with chemotherapy, and the authors recommend its use as preoperative adjunct therapy in patients who present with stage III and IV (Mo) disease.

Adult↗
PubMed1985

Locus coeruleus lesions in the rat enhance the antinociceptive potency of centrally administered clonidine but not morphine.

The nucleus locus coeruleus (LC) has been implicated in the descending inhibition of spinal nociceptive dorsal horn neurons, spinal nociceptive reflexes and in the antinociception produced by morphine. To further explore the involvement of the LC in antinociception, bilateral electrolytic lesions in the LC were made in adult male Sprague-Dawley rats. Lesions in the LC did not alter the antinociception produced by morphine (2.5 and 5 micrograms) administered in the periaqueductal gray in either the tail-flick (TF) or hot-plate (HP) tests when tested 7 and 14 days after the lesions. Baseline nociceptive thresholds in the TF and HP tests likewise were not affected at 7 or 14 days post-lesion. In contrast, the antinociceptive potency of clonidine administered intrathecally on day 13 post-lesion was enhanced significantly in the TF test; the antinociceptive ED50 of the LC lesion group was 0.52 micrograms whereas that of the sham lesion group was 2.29 micrograms. The antinociceptive potency of clonidine administered systemically (750 and 500 micrograms/kg, s.c.) was also enhanced in the LC lesion group in the TF but not the HP test. Norepinephrine (NE) in the lumbar spinal cord was correlated negatively and significantly with the extent of destruction of the LC. The lumbar spinal content of NE was reduced maximally at 12 days post-lesion (to 56% of control). The binding of [3H]clonidine in the lumbar spinal cord was slightly greater in the LC lesion than sham lesion group; the Bmax values were 42.4 fmol/mg protein and 35.5 fmol/mg protein for the LC lesion and sham lesion groups, respectively. It is suggested that the LC participates in the descending inhibition of spinal nociceptive transmission and that this inhibition may be mediated in the spinal cord by alpha-2 adrenoceptors located postsynaptically with respect to the NE terminals of the spinopetal LC efferents.

Animals↗
PubMed1985

Group B streptococci colonization among Saudi women in labor and neonatal acquisition.

Rates of high vaginal Group B Streptococcus colonization and the perinatal transmission were determined in 260 Saudi women admitted for delivery to the Obstetrical Unit of the King Fahd Hospital of the University, Al-Khobar. Of these women, 24 mothers in labour had vaginal colonization (9.2%). Three neonates acquired Group B Streptococci soon after birth on more than one body site and the perinatal transmission rate was 12.5%. Implication of these findings are reviewed.

Female↗
PubMed1985

Socioeconomic and demographic characteristics of induced abortion cases.

The age, parity, marital and socioeconomic status, education, religion, profession and the period of gestation of 200 patients who applied for legal abortions are analyzed. In this study 74% of the women were more than 20 years of age, 75% had attended secondary school, 63% were students or clerks, 53% came from lower- or middle-class families, 40% were Roman Catholics, 45% were unmarried, 40% were nulliparous and 57% had little or no knowledge of contraception.

Abortion Applicants↗
PubMed1984

Failure to produce a non-opioid foot shock-induced antinociception in rats.

Brief continuous foot shock reportedly produces a naloxone-insensitive and thus non-opioid form of antinociception. In the present study, current intensity and duration of foot shock were varied: lower current intensities (0.5 or 1 mA) failed to produce a significant increase in tail flick (TF) latency, while current intensities of 3 mA and 6 mA applied for 2 or 3 min produced significant and long-lasting inhibition of the nociceptive TF reflex. Naloxone pretreatment attenuated significantly the antinociception developed at 3 mA but failed to affect that produced at 6 mA. It was noted, however, that higher current intensities damage the tail and the antinociceptive efficacy of footshock was reevaluated under conditions when the tail of the animal was not allowed to contact the electrified grid during foot shock. A significant short-lasting antinociception was produced only at the 6 mA current intensity. This antinociception could be attenuated by naloxone pretreatment, developed tolerance over time (8 days) and exhibited cross-tolerance with morphine, thus characterizing it as opioid in nature. These results raise the question to what extent damage to the tail contributes to the non-opioid foot shock-induced antinociception assessed using the nociceptive TF reflex.

Animals↗
PubMed1984

Morphine inhibition of the insulin-inducible form of hepatic tyrosine aminotransferase.

Morphine treatment in normal intact rats caused a dose-dependent increase in hepatic tyrosine aminotransferase (TAT) activity, as demonstrable up to 2 hr of exposure to the opioid alkaloid. However, such increase in TAT activity was invariably preceded by a prior decline in the enzyme level, as observed after 15 min of morphine treatment. Such an initial decline in activity was not demonstrable in diabetic animals. Further studies indicate that morphine inhibited the insulin-induced increase in TAT activity, a phenomenon which could be reversed by the opioid antagonist naloxone. The results suggest an opioid control mechanism in the regulation of the insulin-inducible form of TAT and indicate the possibilities of a trophic role of endogenous opiates in gluconeogenesis.

Animals↗
PubMed1984

Interaction of dihydroxy-2-aminotetralin derivatives at sites labelled with [3H]clonidine, [3H]prazosin and [3H]spiperone in rat brain membranes.

The interactions of 5,6- and 6,7-dihydroxy derivatives of 2-aminotetralin with [3H]clonidine and [3H]prazosin as well as with [3H]spiperone binding sites in rat cerebral cortex membrane preparations were investigated. The hydroxy derivatives of 2-aminotetralin tested showed significant interaction with [3H]clonidine as well as with [3H]peiperone binding sites while for [3H]prazosin binding site these agents appeared virtually inactive. For interaction with [3H]clonidine binding site 6,7-dihyroxy substitutions impart greater potency that 5,6-dihydroxy substitutions and N-alkyl substitutions either make no differece or reduce the affinity of these compounds. N-alkyl substitutions, however, markedly enhance the affinity of 5,6-dihydroxy derivatives for interaction with [3H]spiperone binding site. The results suggest that some hydroxy derivatives of aminotetralin have significant interaction with both central alpha 2-adrenoceptor and D2-dopamine receptor systems.

Animals↗
PubMed1984

Role of adrenal steroids on electroacupuncture analgesia and on antagonising potency of naloxone.

Electroacupuncture (EA), a form of transcutaneous electrical stimulation, produces opiate-like antinociception and catalepsy in rats. This effect of EA cannot be produced in hypophysectomised rats, whereas adrenalectomised rats show increased sensitivity. In intact rats, adrenocorticotrophic hormone and dexamethasone have been found to be effective to sensitise the animals to the analgesic effect of EA. Deoxycorticosterone, on the contrary, attenuates this effect. Spironolactone is also effective to potentiate EA response, which is accompanied with severe respiratory depression. Drugs that are known to affect adrenal aldosterone secretion also modulate the effect of EA. Naloxone administration, 15 min prior to the initiation of EA stimulation, potentiates the effect of EA, whereas it counteracts the effect of EA if administered after initiation of EA stimulation. Moreover, this counteracting ability of naloxone increases with the increase in time interval between initiation of stimulation and naloxone challenge. Pretreatment with drugs that impair adrenal mineralocorticoid response to physiological stimuli inhibits the counteracting effect of naloxone. On the contrary, mineralocorticoid supplemented rats show greater sensitivity to naloxone counteraction.

Adrenal Glands↗
PubMed1983

Ovarian steroids and modulation of morphine-induced analgesia and catalepsy in female rats.

The influence of ovarian steroids on modulation of antinociceptive and cataleptic responses to morphine in female rats was evaluated. The sensitivity of the animals to morphine varied at different stages of the estrous cycle. The responses of postpartum and ovariectomized rats to morphine was attenuated. The test doses of estradiol-17 beta or progesterone, either alone or in combination, did not alter this attenuated morphine sensitivity. Testosterone, however, sensitized post-partum as well as ovariectomized rats to morphine. Unlike progesterone, 17-alpha-hydroxy progesterone antagonized testosterone. Collectively these data implicate ovarian testosterone as a physiological modulator of actions of morphine in female rats.

Analgesia↗