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Biomedical subjects

T T Nguyen

Publications and source records attributed to T T Nguyen.

At least 109 records · Page 6Linked to original sources
PubMed1998

Fluoride profiles of perikymata in enamel surfaces of human premolars.

Twenty-five premolars (from Nagoya, Japan < 0.1 parts/10(-6)F in drinking water) were sampled to determine the fluoride content in imbrication lines of Retzius between the grooves and ridges of perikymata on the enamel surface. Eight small windows were formed on each surface in groove and ridge regions using an etched microsampling technique. By using a regression curve, y = ax(-b), fluoride concentrations were compared at depths of 1, 3, 5, 10, 20, 30 and 50 microm in the perikymata regions. Fluoride concentrations increased gradually from the age of 10 to 12 years on the premolar surfaces, but were significantly higher in 12-year-olds or older (erupted teeth) than in 10-year-olds or younger (unerupted teeth). No obvious difference in fluoride concentrations was found between males and females. In the outermost enamel ( < 5 microm depth), fluoride concentrations were significantly higher in the grooves than the ridges of the perikymata. Comparison of the exponential regression coefficients (-b) of the fluoride profiles showed a significant difference between the grooves and ridges. It was concluded that fluoride concentrations and profiles were higher in grooves than in ridges of perikymata, probably because they are naturally porous and are stagnation areas attracting dental plaque.

Acid Etching, Dental↗
PubMed1998

An inverted cAMP response element mediates the cAMP induction of the ovine beta 1-adrenergic receptor gene.

We identified an inverted, functional cAMP response element (CRE) located at--1599 bp relative to the translation start site within the ovine beta 1-adrenergic receptor (beta 1 AR) gene promoter. In transfection studies with SK-N-MC cells, a 40-bp oligonucleotide containing the potential CRE, beta 1 AR-CRE, conferred a 3- to 4-fold increase in luciferase activity mediated by cAMP. The induction was mimicked by co-transfecting the cells with a vector overexpressing the alpha-catalytic subunit of the cAMP-dependent protein kinase (PKA) without treatment, and was blocked by overexpressing a PKA inhibitor (PKI). In electrophoretic mobility shift assays, a discrete binding pattern was shown in cell nuclear extract probed with the 40 bp beta 1 AR-CRE. The binding was shown to be specific and supershifted by addition of a CRE binding protein (CREB-1) antibody. These data demonstrate that cAMP mediates the induction of beta 1 AR gene expression by interacting with an inverted CRE within the promoter region. This is the first reported functional CRE among all beta 1 AR genes.

Animals↗
PubMed1998

Penicillin vs. erythromycin in the treatment of diphtheria.

In an open-label, randomized trial, 44 Vietnamese children with diphtheria were given penicillin therapy (intramuscular benzylpenicillin, 50,000 U/[kg.d] for 5 days and then oral penicillin, 50 mg/[kg.d] for 5 days), and 42 were given erythromycin therapy (50 mg/[kg.d] orally for 10 days). There were no differences in times to membrane clearance or bacteriologic clearance, but median times to fever clearance were 27 hours (95% confidence interval [CI], 19-30; range, 0-124 hours) for penicillin recipients and 46 hours (95% CI, 34-54; range, 0-148 hours) for erythromycin recipients (P = .0004). In the penicillin group, acute treatment failed for one patient, and one patient relapsed. Three patients in the penicillin group developed diphtheritic myocarditis as evidenced by abnormal electrocardiograms. Erythromycin did not cause prolongation of the QT interval corrected for heart rate. Cultures of specimens from 15 patients (17.4%) were positive for toxigenic Corynebacterium diphtheriae. All isolates were susceptible to penicillin, but for isolates (27%), all of which were from patients who received penicillin treatment, were resistant to erythromycin (minimum inhibitory concentrations, > 64 mg/L). Penicillin is recommended as first-line treatment for diphtheria in Vietnam.

Adolescent↗
PubMed1998

Effects of insulin on wound healing.

BACKGROUND: Insulin plus glucose, given for 7 days to hypermetabolic burn patients, has been shown to stimulate limb protein anabolism. We hypothesized that insulin plus glucose given to burn patients would also stimulate wound healing. METHODS: Six patients with burns >40% total body surface area were randomized to receive insulin or placebo in a crossover study during the healing of their first and second donor sites. Insulin treatment was titrated at 25 to 49 U/h to achieve a plasma insulin level of 400 to 900 microU/mL for 7 days. Patients receiving insulin received dextrose 50 at 20 to 50 mL/h, titrated to maintain euglycemia. Donor-site biopsies were taken at 7 days and evaluated by three observers blinded to the treatment. RESULTS: The mean (+/-SD) donor-site healing time was reduced from 6.5 +/- 1.0 days with placebo to 4.7 +/- 1.2 days during insulin infusion (p < 0.05). Laminin showed intense staining along the basal lamina and blood vessels. Collagen type IV staining also increased after insulin therapy compared with placebo. CONCLUSION: Data indicate that high doses of insulin and glucose can be safely administered to massively burned patients to improve wound matrix formation.

Adolescent↗
PubMed1998

Light regulation of Fed-1 mRNA requires an element in the 5' untranslated region and correlates with differential polyribosome association.

Light regulation of Fed-1 mRNA abundance in the leaves of green plants is primarily a post-transcriptional process. Previously, we have shown that the Fed-1 mRNA light response requires an open reading frame, indicating that the light regulation of the mRNA depends on its concurrent translation. We now show that light-induced increases in Fed-1 mRNA abundance are associated with increases in polyribosome association that require both a functional AUG and a normal Fed-1 translational start context. We also present evidence that light regulation of Fed-1 mRNA levels requires more than efficient translation per se. Substitution of the efficiently translated tobacco mosaic virus Omega 5' untranslated region resulted in a loss of Fed-1 light regulation. In addition, we identified a CAT T repeat element located near the 5' terminus of the Fed-1 5' untranslated region that is essential for light regulation. We introduced two different mutations in the CAT T repeat element, but only one of these substitutions blocked the normal light effect on polyribosome association, whereas both altered dark-induced Fed-1 mRNA disappearance. The element may thus be important for Fed-1 mRNA stability rather than polyribosome loading. We propose a model in which Fed-1 mRNA is relatively stable when it is associated with polyribosomes in illuminated plants but in darkness is not polyribosome associated and is thus rapidly degraded by a process involving the CAT T repeat element.

Codon↗
PubMed1998

Quantitation of bacteria in blood of typhoid fever patients and relationship between counts and clinical features, transmissibility, and antibiotic resistance.

Salmonella typhi was isolated from 369 and Salmonella paratyphi A was isolated from 6 of 515 Vietnamese patients with suspected enteric fever. Compared with conventional broth culture of blood, direct plating of the buffy coat had a diagnostic sensitivity of 99.5% (95% confidence interval [CI], 97.1 to 100%). Blood bacterial counts were estimated by the pour plate method. The median S. typhi count in blood was 1 CFU/ml (range, <0.3 to 387 CFU/ml), of which a mean of 63% (95% CI, 58 to 67%) were intracellular. The mean number of bacteria per infected leukocyte was 1.3 (interquartile range [IQR], 0.7 to 2.4) CFU/cell (n = 81). Children (< 15 years old; n = 115) had higher median blood bacterial counts than adults (n = 262): 1.5 (range, <0.3 to 387) versus 0.6 (range, <0.3 to 17.7) CFU/ml (P = 0.008), and patients who excreted S. typhi in feces had higher bacteremias than those who did not: a median of 3 (range, <0.3 to 32) versus 1 (range, <0.3 to 68) CFU/ml (P = 0.02). Blood bacterial counts declined with increasing duration of illness (P = 0.002) and were higher in infections caused by multidrug-resistant S. typhi (1.3 [range, <0.3 to 387] CFU/ml; n = 313) than in infections caused by antibiotic-sensitive S. typhi (0.5 [range, <0.3 to 32] CFU/ml; n = 62) (P = 0.006). In a multivariate analysis this proved to be an independent association, suggesting a relationship between antibiotic resistance and virulence in S. typhi.

Adolescent↗
PubMed1998

Comparison of intestinal folate carrier clone expressed in IEC-6 cells and in Xenopus oocytes.

We recently identified a cDNA clone from mouse small intestine, which appears to be involved in folate transport when expressed in Xenopus oocytes. The open reading frame of this clone is identical to that of the reduced folate carrier (RFC) (K. H. Dixon, B. C. Lanpher, J. Chiu, K. Kelley, and K. H. Cowan. J. Biol. Chem. 269: 17-20, 1994). The characteristics of this cDNA clone [previously referred to as intestinal folate carrier 1 (IFC-1)] expressed in Xenopus oocytes, however, were found to be different from the characteristics of folate transport in native small intestinal epithelial cells. To further study these differences, we determined the characteristics of RFC when expressed in an intestinal epithelial cell line, IEC-6, and compared the findings to its characteristics when expressed in Xenopus oocytes. RFC was stably transfected into IEC-6 cells by electroporation; its cRNA was microinjected into Xenopus oocytes. Northern blot analysis of poly(A)+ RNA from IEC-6 cells stably transfected with RFC cDNA (IEC-6/RFC) showed a twofold increase in RFC mRNA levels over controls. Similarly, uptake of folic acid and 5-methyltetrahydrofolate (5-MTHF) by IEC-6/RFC was found to be fourfold higher than uptake in control sublines. This increase in folic acid and 5-MTHF uptake was inhibited by treating IEC-6/RFC cells with cholesterol-modified antisense DNA oligonucleotides. The increase in uptake was found to be mainly mediated through an increase in the maximal velocity (Vmax) of the uptake process [the apparent Michaelis-Menten constant (K(m)) also changed (range was 0.31 to 1.56 microM), but no specific trend was seen]. In both IEC-6/RFC and control sublines, the uptake of both folic acid and 5-MTHF displayed 1) pH dependency, with a higher uptake at acidic pH 5.5 compared with pH 7.5, and 2) inhibition to the same extent by both reduced and oxidized folate derivatives. These characteristics are very similar to those seen in native intestinal epithelial cells. In contrast, RFC expressed in Xenopus oocytes showed 1) higher uptake at neutral and alkaline pH 7.5 compared with acidic pH 5.5 and 2) higher sensitivity to reduced compared with oxidized folate derivatives. Results of these studies demonstrate that the characteristics of RFC vary depending on the cell system in which it is expressed. Furthermore, the results may suggest the involvement of cell-or tissue-specific posttranslational modification(s) and/or the existence of an auxiliary protein that may account for the differences in the characteristics of the intestinal RFC when expressed in Xenopus oocytes compared with when expressed in intestinal epithelial cells.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation.

These studies were designed to examine whether the respiratory quotient (RQ) of leg tissue (primarily skeletal muscle) would increase to a greater degree in women than in men during meal ingestion. We found that mean leg and systemic RQ values were similar in men under both basal and fed conditions, whereas the agreement was poor in women. In women, leg RQ values tended to be greater than the systemic RQ, whereas splanchnic RQ values tended to be lower than the systemic RQ. The possibility that measurement imprecision accounted for the different findings in women could not be excluded because the arteriovenous blood O2 differences were almost twice as great in men as in women (53.7 +/- 5.4 vs. 28.6 +/- 2.9 ml of O2/l, respectively; P < 0.01), as were venoarterial blood CO2 differences. The smaller arteriovenous differences in women appeared to limit our ability to accurately measure their leg RQ values. O2 uptake relative to leg fat-free mass (FFM) was not different between men and women, whereas leg blood flow relative to leg FFM was greater in women than in men (55 +/- 3 vs. 39 +/- 2 ml.kg FFM-1.min-1, respectively; P < 0.001). These findings were confirmed by examining data from other studies conducted in our laboratory to create a larger data set. We conclude that resting leg blood flow in women is greater (relative to FFM) than in men, making it more difficult to accurately measure leg RQ in women.

Adult↗
PubMed1998

Direct measurement of the contributions of type I and type II 5'-deiodinases to whole body steady state 3,5,3'-triiodothyronine production from thyroxine in the rat.

Production of T3 from T4 in tissues is catalyzed by two 5'-deiodinases, type I (D1) and type II (D2), but the quantitative contribution of each pathway to whole body T3 production is not well established. In the presence of propylthiouracil (PTU), D1, but not D2, can be effectively blocked, providing an experimental probe for addressing this problem. Decades ago, this approach provided indirect estimates ranging from 23-44% contribution by D2, based on plasma T3 appearance rate comparisons (PAR3 = PCR3 [T3]p) in periodically T4-injected athyreotic rats vs. controls. Two, more recent studies, using constant infusions of T4 for replacement, achieved 22% and 65% estimates, respectively, from PAR3 comparisons. We have revisited this problem more directly and precisely, with two major differences in experiment design. We used direct whole body steady state measurements of T3 production, instead of indirect plasma-only data (PAR3). We also used (euthyroid) physiological doses of both T4 (0.9 microg/day x 100 g BW) and T3 (0.15 microg/day x 100 g BW) for replacement in two thyroidectomized rat groups, instead of T4 only, in a 7-day constant steady state, dual tracer infusion protocol. The first group also had chronically implanted 150-mg PTU pellets (TXR-PTU); the other had implanted 0.1 N NaOH placebo pellets (TXR-EU); each delivered their product at constant rates. A third euthyroid intact group was used as the controls. The completeness of D1 inhibition was ascertained in a fourth group, identically treated with 150-mg PTU pellets, in which negligible D1 activity was found in liver and kidney using labeled rT3 as substrate for the 5'-D assays and minimal (1 mM) dithiothreitol as cofactor. In the TXR-PTU group, the percentage of T4 converted to T3 was 11.8%, compared with 23.4% (P < 0.0005) in the TXR-EU group, and 22.7% (P = NS) in controls. Thus, in euthyroid steady state, D2 contributes about half of the T3 produced from T4.

Animals↗
PubMed1998

Hyperlipidemia and diabetes mellitus.

The increased risk of coronary artery disease in subjects with diabetes mellitus can be partially explained by the lipoprotein abnormalities associated with diabetes mellitus. Hypertriglyceridemia and low levels of high-density lipoprotein are the most common lipid abnormalities. In type 1 diabetes mellitus, these abnormalities can usually be reversed with glycemic control. In contrast, in type 2 diabetes mellitus, although lipid values improve, abnormalities commonly persist even after optimal glycemic control has been achieved. Screening for dyslipidemia is recommended in subjects with diabetes mellitus. A goal of low-density lipoprotein cholesterol of less than 130 mg/dL and triglycerides lower than 200 mg/dL should be sought. Several secondary prevention trials, which included subjects with diabetes, have demonstrated the effectiveness of lowering low-density lipoprotein cholesterol in preventing death from coronary artery disease. The benefit of lowering triglycerides is less clear. Initial approaches to lowering the levels of lipids in subjects with diabetes mellitus should include glycemic control, diet, weight loss, and exercise. When goals are not met, the most common drugs used are hydroxymethylglutaryl coenzyme A reductase inhibitors or fibrates.

Coronary Disease↗
PubMed1998

Effect of thyroid hormone replacement on lipoprotein(a), lipids, and apolipoproteins in subjects with hypothyroidism.

OBJECTIVE: To study the effect of thyroid hormone replacement on total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I and B-100, and lipoprotein(a) [Lp(a)] in subjects with hypothyroidism. MATERIAL AND METHODS: In 17 patients with clinical primary hypothyroidism, studies were done before and after thyroid hormone replacement therapy. Free thyroxine and thyrotropin were determined by chemiluminescent assay. Total cholesterol and triglycerides were measured by enzymatic methods, and HDL-C was measured after dextran sulfate-MgCl2 precipitation. Apolipoprotein A-I and B-100 were assayed by immunonephelometry. For measurement of Lp(a), we used a sequential sandwich enzyme-linked immunosorbent assay. RESULTS: After levothyroxine treatment, the mean concentration of thyrotropin decreased from 91.4 to 3.7 microIU/mL, and free thyroxine increased from 0.5 to 1.2 ng/ dL. Total cholesterol, triglycerides, HDL-C, low-density lipoprotein cholesterol, and apolipoprotein A-I and B-100 decreased after thyroid hormone replacement therapy. Lp(a) levels also decreased significantly (P<0.05) after treatment, from a mean of 33.4 to 25.6 mg/dL. CONCLUSION: Hypothyroidism is associated with an increase in total cholesterol, triglycerides, HDL-C, apolipoprotein A-I and B-100, and Lp(a). A reduction in lipid and lipoprotein levels after thyroid hormone replacement in our study cohort resulted in a less atherogenic profile.

Apolipoproteins↗
PubMed1998

Human orosomucoid (ORM1) subtyping: further population genetic data and reports on the feasibility to type aged blood samples and stains.

Genetic polymorphism of serum orosomucoid (ORM1) was investigated in 1072 unrelated German Caucasians using isoelectric focusing followed by Western blotting and EIA. The estimated allele frequencies were ORM1 *F1 = 0.5690, ORM1 *S = 0.3927, ORM1 *F2 = 0.0368, ORM1 *F2S = 0.0009 and ORM1 *F5 = 0.0005. The method was successfully applied to determine ORM1 phenotypes in aged blood samples and blood stains. The results indicated that the ORM protein is a informative and remarkably robust blood group system.

Alleles↗
PubMed1997

Anti-IgM-induced growth inhibition and apoptosis are independent of ornithine decarboxylase in Ramos cells.

Ornithine decarboxylase (ODC) is a key enzyme involved in polyamine production and is thought to regulate growth and apoptosis in multiple cell systems. A potential link between ODC and growth may involve the action of an oncogene c-myc which is thought to transcriptionally regulate ODC. We have examined the involvement of ODC in anti-IgM-induced growth inhibition and apoptosis in Burkitt's lymphoma cells. Inhibitors of ODC such as difluoromethylornithine (DFMO) completely blocked ODC activity, resulting in growth inhibition but not apoptosis. Addition of putrescine, the product of ODC enzymatic action, to Ramos cells had only a minor effect on growth, did not cause apoptosis, did not augment or block anti-IgM-mediated growth inhibition and apoptosis, but did reverse DFMO-mediated growth inhibition. Anti-IgM treatment of Ramos cells, which markedly decreased c-myc mRNA and protein, caused a paradoxical increase in ODC mRNA level as well as ODC enzymatic activity and increased cellular levels of putrescine. DFMO and putrescine did not alter c-myc mRNA levels directly, nor did they have any affects on anti-IgM-mediated down-regulation of c-myc mRNA. TNF-alpha, which inhibited anti-IgM-mediated apoptosis, did not inhibit either anti-IgM or DFMO-mediated inhibition of growth. These agents were without effect on ODC activity itself or on the anti-IgM-mediated increase in ODC activity. From these studies we conclude that ODC inhibition affects growth but is unrelated to the induction of apoptosis. Both anti-IgM-mediated inhibition of growth and induction of apoptosis are independent of ODC. Thus two distinct pathways for growth regulation are present: one in which ODC and polyamines are important and the other cell surface receptor-mediated (sIg) which is independent of ODC and polyamines.

Apoptosis↗
PubMed1997

Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] levels have been associated with the presence of atherosclerotic disease. However, the results of prospective studies of Lp(a) and cardiovascular disease have been contradictory. METHODS AND RESULTS: From 1968 through 1982, lipoprotein analysis was performed in 11,335 Olmsted County residents. Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a) levels based on electrophoretic pattern. Lp(a) bands were scored from 0 (absent) to 3 (increased). A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a) determinations were followed up for 14 years for development of coronary artery disease (CAD) and cerebrovascular disease (CVD). During 131,330 person-years of follow-up, there were 1848 CAD events and 841 CVD events. Age, diabetes, hypertension, cholesterol, and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women. There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a) levels for men and women. For Lp(a) level 3, the hazard ratio was 1.9 (range, 1.3 to 2.9) in women and 1.6 (range, 1.0 to 2.5) in men. The adjusted hazard ratio for CVD showed an irregular association with Lp(a) levels in men and no association in women. CONCLUSIONS: In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years, Lp(a) was a significant predictor of risk of future CAD. Lp(a) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women.

Adult↗
PubMed1997

Majonoside-R2 reverses social isolation stress-induced decrease in pentobarbital sleep in mice: possible involvement of neuroactive steroids.

Majonoside-R2 (MR2) is a major ocotillol-type saponin constituent of Vietnamese ginseng. We investigated the effect of MR2 on the social isolation stress-induced decrease in pentobarbital sleep in mice, and elucidated the possible involvement of neurosteroidal sites of the GABA(A) receptor complex in the pharmacological activity of MR2. MR2 (3.1-6.2 mg/kg, i.p. or 5-10 microg, i.c.v.) dose-dependently reversed the decrease in pentobarbital sleep caused by social isolation stress to the level of sleep in the group-housed mice, but it had no effect on pentobarbital sleep in group-housed mice. Allotetrahydrodeoxycorticosterone (5alpha-pregnane-3alpha,21-diol-20-one, allo-THDOC; 12.5 microg, i.c.v.), the positive allosteric modulator of the GABA(A) receptor, and alpha-helical CRF(9-41) (alpha hCRF; 25 microg, i.c.v.), the corticotropin-releasing factor (CRF) antagonist, also reversed the decrease in pentobarbital sleep caused by social isolation stress. The reversing effects of i.c.v. MR2 and i.c.v. allo-THDOC on the decrease in pentobarbital sleep in isolated mice were significantly attenuated by pregnenolone sulfate (10 microg, i.c.v.), the steroidal negative allosteric modulator of the GABA(A) receptor. In contrast, when injected i.c.v., MR2, as well as allo-THDOC and alpha hCRF, significantly reversed the decrease in pentobarbital sleep induced by pregnenolone sulfate (10 microg, i.c.v.) and CRF (10 microg, i.c.v.) in group-housed mice. These results suggest that the reversing effect of MR2 on the social isolation stress-induced decrease in pentobarbital sleep is mediated by the neurosteroid site on the GABA(A) receptor complex in mice.

Animals↗
PubMed1997

Involvement of supraspinal GABA receptors in majonoside-R2 suppression of clonidine-induced antinociception in mice.

Majonoside-R2 (MR2) is a major constituent of Vietnamese ginseng (Panax vietnamensis, Ha et Grushv. Araliaceae) that is known to exhibit antagonistic activity against opioid-induced antinociception. In this study, we investigated the effect of MR2 on the antinociception caused in mice by the alpha2-adrenoceptor agonist clonidine, and elucidated the role of supraspinal GABAergic systems in this effect of MR2. The systemic administration of clonidine (0.5-2.5 mg/kg, s.c.) dose-dependently suppressed the nociceptive response of mice in the tail-pinch and hot-plate tests. The intraperitoneal (i.p.), intracerebroventricular (i.c.v.) or intrathecal (i.t.) administration of idazoxan (a selective alpha2-adrenoceptor antagonist) significantly antagonized the antinociceptive effect of clonidine in both tests. MR2 administered systemically (1.5-6.2 mg/kg, i.p.) or centrally (5-10 microg/mouse, i.c.v. or i.t.) dose-dependently antagonized the clonidine (1 mg/kg, s.c.)-induced antinociception in the tail-pinch test but not in the hot-plate test. The antagonistic effect of i.c.v. MR2 on the systemic clonidine-induced antinociception in the tail-pinch test was significantly reversed by i.c.v. administrations of the selective benzodiazepine receptor antagonist flumazenil (5 microg/mouse) and the GABA(A) antagonist picrotoxin (0.25 microg/mouse). These results suggest that the supraspinal GABA(A)/benzodiazepine receptors are involved in the antagonistic effect of MR2 on the clonidine-induced antinociception in the tail-pinch test in mice.

Adrenergic alpha-Agonists↗
PubMed1997

Involvement of supraspinal GABA-ergic systems in clonidine-induced antinociception in the tail-pinch test in mice.

We investigated the involvement of supraspinal GABAergic systems in the antinociceptive effect of clonidine using the tail-pinch test in mice. Muscimol (31.2-250 ng/mouse, i.c.v.) and R(+)-baclofen (10-100 ng/mouse, i.c.v.), selective agonists for the GABA(A) and GABA(B) receptors, respectively, significantly attenuated the antinociceptive effect of subcutaneously (s.c.) administered clonidine (1 mg/kg) in a dose-dependent manner. The attenuating effect of muscimol (62.5 ng/mouse, i.c.v.) on the clonidine-induced antinociception was significantly blocked by the GABA(A) antagonists bicuculline (100-400 ng/mouse, i.c.v.) and picrotoxin (250 ng/mouse, i.c.v.) but not by the GABA(B) antagonist 2-hydroxysaclofen (10 microg/mouse, i.c.v.). On the other hand, the attenuating effect of R(+)-baclofen (50 ng/mouse, i.c.v.) was blocked by the coadministration with 2-hydroxysaclofen (20 microg/mouse), but was not affected by the coadministration with bicuculline (400 ng/mouse). These results indicate that both supraspinal GABA(A) and GABA(B) receptors play inhibitory roles in the antinociception caused by systemically administered clonidine.

Adrenergic alpha-2 Receptor Agonists↗