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D D Godse

Publications and source records attributed to D D Godse.

At least 19 recordsLinked to original sources
PubMed1986

Further characterization of brain 3,4-dihydroxyphenylethyleneglycol (DHPG) formation: dependence on noradrenergic activity and site of formation.

The dependence of brain and plasma 3,4-dihydroxyphenylethyleneglycol (DHPG) formation upon CNS noradrenergic neutronal activity was evaluated following manipulations that are known to alter the firing rate of the locus coeruleus (LC) neurons and as a consequence, noradrenaline (NA) release and turnover. In addition, the relative degree of intraneuronal formation of brain DHPG was assessed by studying the metabolism of released NA during uptake inhibition. Electrical stimulation of the LC for 20 min induced an increase in rat cortical (40-42%), hypothalamic (22-29%) and plasma (68-79%) total DHPG and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels. Two hours following administration of the alpha-2 adrenoceptor antagonist yohimbine (10 mg/kg, i.p.), rat brain cortical conjugated DHPG and MHPG as well as free MHPG concentrations were increased whereas cortical free DHPG levels remained unchanged. The same treatment also increased plasma total DHPG and MHPG levels. In mice given the NA uptake inhibitor desipramine (10 mg/kg, i.p.) 2 h prior to sacrifice, brain free DHPG and MHPG concentrations were significantly reduced by 30 and 40%, respectively, whereas yohimbine (1-20 mg/kg, i.p.) induced a dose-dependent increase in brain DHPG (60-80%) and MHPG (60-220%) concentrations. Pretreatment with desipramine (10 mg/kg, i.p.) 30 min prior to yohimbine reduced, in rat, or abolished, in mice, the yohimbine-induced elevation of brain DHPG levels. In contrast, desipramine augmented the effect of yohimbine on brain MHPG levels resulting in a shift to the left of the dose response curves. These findings indicate that brain and plasma DHPG levels are sensitive to changes in brain noradrenergic neuronal impulse flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Elevated 3,4-dihydroxyphenylethyleneglycol (DHPG) excretion in dexamethasone resistant depressed patients.

Urinary and plasma DHPG and MHPG were estimated in patients with MADD and showing DST non-suppression as compared to those with normal suppression. Day and night 12h urine collections and morning plasma samples were analyzed by GC-MS for total MHPG and DHPG and free MHPG levels. Urinary DHPG excretion was significantly elevated in DST non-suppressors compared to suppressors, but no differences were found in urinary MHPG or plasma glycol levels. Elevated DHPG excretion in DST non-suppressors suggests that increased peripheral sympathetic NE activity occurs in association with dexamethasone resistance in MADD.

Adult↗
PubMed1985

Studies on the utility of urinary 3,4-dihydroxyphenylethylene-glycol (DHPG) measurement.

The utility of urinary DHPG measurement as an index of NE function was evaluated in an animal model by determining its excretion following pharmacological manipulations that are known to alter noradrenergic activity. Acute desipramine (DMI) administration (10 mg/kg, i.p., b.i.d.) significantly reduced urinary DHPG (-26%) but not MHPG (-18%) excretion. Acute yohimbine administration (5 mg/kg, i.p., b.i.d.) significantly increased urinary DHPG and MHPG levels to a similar extent (+46%). These findings suggest that urinary DHPG levels also provide a sensitive indicator reflecting changes in NE neuronal activity. Further, DHPG may be a better measure of NE metabolism than MHPG to assess the efficiency of the NE neuronal uptake system.

Animals↗
PubMed1984

Formation and clearance of norepinephrine glycol metabolites in mouse brain.

To determine the degree of conversion of 3,4-dihydroxyphenylethyleneglycol (DHPG) to 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the amount of DHPG eliminated unchanged from the brain, we have examined the kinetics of formation and disappearance of mouse brain MHPG and DHPG following clorgyline (10 mg/kg, i.p.) and/or tropolone (75 mg/kg, i.p.) treatment. During the first 10 min after tropolone, brain DHPG levels accumulated linearly at a rate of 1,300 pmol/g/h, whereas MHPG disappeared exponentially at a rate of 411 pmol/g/h. Following clorgyline administration, brain DHPG declined exponentially at a rate of 1,240 pmol/g/h. In contrast, the elimination of MHPG became a first-order process only when catechol-O-methyltransferase (COMT) was also inhibited in addition to monoamine oxidase. Thus, combined clorgyline and tropolone treatment resulted in an exponential decline of MHPG levels at a rate of 524 pmol/g/h, whereas DHPG levels were slightly but significantly elevated compared to control values. When the animals were treated with pargyline (75 mg/kg, i.p.) in combination with clorgyline and tropolone, brain DHPG and MHPG disappeared at rates of 40 and 660 pmol/g/h, respectively. The above observations suggest that mouse brain DHPG is cleared primarily through O-methylation with minimal direct elimination from brain. Assuming the disposition and clearance of norepinephrine metabolites are similar in mouse and human brain, peripherally measured DHPG in humans is likely derived principally from extracerebral sources and reflects peripheral sympathetic function.

Animals↗
PubMed1983

Metabolic fate of 3,4-dihydroxyphenylethyleneglycol (DHPG) in mouse brain.

Mouse brain DHPG and MHPG turnover rates were estimated by determining their initial rates of disappearance or accumulation following MAO and/or COMT inhibition. Similar turnover estimates of brain DHPG were obtained following MAO or COMT inhibition, which were comparable to the estimated NE turnover obtained from its initial accumulation following MAO plus COMT inhibition. It was estimated that negligible amounts of DHPG were eliminated directly from brain, the majority being cleared through O-methylation. These findings indicate that mouse brain NE is primarily cleared through DHPG formation followed by O-methylation, and also suggest that brain DHPG turnover is more indicative of NE turnover.

Animals↗
PubMed1983

Rat brain norepinephrine metabolism: substantial clearance through 3,4-dihydroxyphenylethyleneglycol formation.

To assess whether the metabolic clearance of rat brain norepinephrine (NE) through 3,4-dihydroxyphenylethyleneglycol (DHPG) formation is quantitatively comparable or greater than through 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) production, we studied the accumulation rates of conjugated DHPG and MHPG following probenecid administration in whole brain as well as in several brain regions. Administration of increasing doses of probenecid (100-500 mg/kg, i.p.) 1.5 h before sacrifice produced a dose-dependent increase of conjugated DHPG and MHPG levels. The maximum increment of these conjugated metabolites occurred at a dose of 300 mg/kg or higher. During the first hour following probenecid administration (300 mg/kg, i.p.), rat brain conjugated DHPG and MHPG levels accumulated linearly at a rate of 646 and 319 pmol/g/h, respectively. With the probenecid technique, the estimated appearance rates of conjugated DHPG significantly exceeded those of conjugated MHPG in hypothalamus, midbrain, brainstem, hippocampus, and cerebral cortex. These results clearly indicate that under resting conditions, formation and efflux of conjugated DHPG is the major route of metabolic clearance of rat brain NE.

Animals↗
PubMed1982

Simultaneous determination of norepinephrine, dopamine and serotonin in rat brain regions by ion-pair liquid chromatography on octyl silane columns and amperometric detection.

A highly sensitive and specific ion-pair liquid chromatography-electrochemical detection method is described for the simultaneous determination of rat brain regional norepinephrine, dopamine and serotonin levels using octylsilane (C8) columns. These amines were first isolated from tissue homogenates by adsorption on Amberlite CG-50 resin followed by separation on RP-8 columns with a mobile phase consisting of 0.05 M NaH2PO4 (pH 3.0) 0.02 mM EDTA, 1 mM heptanesulphonate-methanol (92:8, v/v) at 1.8 ml/min. Using 3,4-dihydroxybenzylamine as the internal standard, tissue recoveries (mean +/- S.D.) for norepinephrine, dopamine and serotonin were 87.5 +/- 2.6%, 61.8 +/- 10.5% and 72.9 +/- 7.5%, respectively. Assay sensitivities were sufficient for reliable quantitation of at least 200 pg of these compounds in a brain sample. The procedure is readily adaptable to determination of brain epinephrine and normetanephrine levels, as well. Finally, the reversed-phase system employed is highly flexible in that the same column and mobile phase conditions may be used for assay of biogenic amine metabolites.

Animals↗
PubMed1981

Rat brain and plasma norepinephrine glycol metabolites determined by gas chromatography-mass fragmentography.

A gas chromatographic-mass fragmentographic (GC-MF) procedure is described for the simultaneous quantitation of 3,4-dihydroxyphenylethyleneglycol (DHPG) and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in brain tissue and plasma. DHPG and MHPG were assayed as their respective acetyl-trifluoroacyl esters, using [2H2]DHPG and [2H3]MHPG as internal standards. Assay sensitives of at least 1 ng per sample were attainable for the quantitation of free glycols, whereas for determination of total DHPG, assay sensitivity was 2.5 ng. Whole rat brain total (99.2 +/- 4.11 ng/g) and free (13.0 +/- 1.14 ng/g) DHPG concentrations were similar to respective total (86.0 +/- 3.70 ng/g) and free (12.3 +/- 0.41 ng/g) MHPG levels. Total DHPG concentrations exceeded total MHPG levels in hypothalamus (3.0:1), midbrain (1.4:1), pons plus medulla (1.3:1), and hippocampus (1.5:1), whereas in other brain regions the levels of these metabolites were similar. In plasma, however, total DHPG levels were only 20% as high as MHPG concentrations. In mouse brain, DHPG and MHPG occurred almost entirely in free form (greater than 90%), but total DHPG levels were only 50% as high as respective MHPG concentrations. These results emphasize the substantial formation of DHPG compared with MHPG in rat and mouse brain and suggest that DHPG formation and efflux may be of equal or greater importance than MHPG in the metabolic clearance of CNS norepinephrine in some species.

Animals↗
PubMed1981

Postmortem stability of brain 3-methoxy-4-hydroxyphenylethyleneglycol and 3,4-dihydroxyphenylethyleneglycol in the rat and mouse.

To assess the postmortem stability of brain 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) levels, groups of rats and mice were killed by cervical dislocation and left at either 21 degrees or 4 degrees C for intervals of up to 24 h until removal and freezing of whole brain. Whole brain free and total MHPG and DHPG levels were determined simultaneously by gas chromatography-mass fragmentography (GC-MF). By 2 h death, statistically significant decrements occurred in rat brain free DHPG (20%), total MHPG (21%), and total DHPG (11%) at 4 degrees C, but free MHPG increased significantly (50%) compared with controls. At 21 degrees C, rat brain total MHPG increased compared with controls at 2 h (15%) but decreased at 4 h (15%) and 8 h (15%), whereas free MHPG levels were increased at these times. Although brain total and conjugated DHPG levels showed little change, free DHPG levels were reduced at all times. In mouse brain no significant changes occurred in free MHPG and DHPG by 24 h at 4 degrees C. At 21 degrees C, mouse brain DHPG levels decreased whereas MHPG concentrations increased over the 8-h period of study. These findings demonstrate the occurrence of significant postmortem time- and temperature-dependent changes in brain MHPG and DHPG concentrations and indicate caution in the interpretation of changes in these metabolites in studies employing human postmortem brain tissue.

Animals↗
PubMed1979

Bufotenine esters.

Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl esters of bufotenine were prepared for future pharmacological evaluation. Unexpectedly, it was found that these esters all possess a relatively high affinity for the serotonin receptors of the isolated rat stomach fundus preparation. A semiquantitative chromatographic measurement of ester hydrolysis suggests that extensive hydrolysis of the esters to bufotenine does not occur under the conditions of the affinity assay.

Animals↗
PubMed1978

5-Hydroxytryptophol in human cerebrospinal fluid: quantitative determination by gas chromatography-mass spectrometry using a deuterated internal standard.

Procedures for the quantification of 5-hydroxyindole-3-ethanol, or 5-hydroxy-tryptophol (5-HTOL), in human cerebrospinal fluid are described. 5-HTOL was determined as its di-pentafluorpropionyl derivative. Deuterium labelled 5-hydroxyindole-3-ethanol-a,a,b,b-d4 (5-HTOL-d4) was used as internal standard. Mass fragmentography was performed by double ion monitoring each for 5-HTOL and 5-HTOL-d4 and their ratios were determined for specificity. Assay sensitivities of 0.15 ng/ml were achieved using 2.0 ml of cerebrospinal fluid. Free 5-HTOL concentrations in human cerebrospinal fluid were determined to be 0.73 +/- 0.44 ng/ml (mean +/- S.D.) (range 0.33-2.11 ng/ml) from 15 patients with various neurological disorders, and 0.85 +/- 0.30 ng/ml (range 0.48-1.32 ng/ml) from 9 subjects who complained of low back pain but did not show signs of neurological illnesses.

Chromatography, Gas↗
PubMed1978

Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice.

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.

Animals↗