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PubMed1982

Effect of 3,4-dihydroxyphenylpyruvic acid on the metabolism of L-DOPA in isolated perfused rat liver.

The effect of 3,4-dihydroxyphenylpyruvic acid (DHPPA) on the hepatic metabolism of L-DOPA was investigated in isolated perfused rat liver. DHPPA decreased the initial hepatic extraction and prolonged the elimination half-life of L-DOPA when they were added simultaneously at the ratio 1:4 (L-DOPA: DHPPA) to the perfusate. At the ratio 1:1 DHPPA had no effect on the elimination half-life, but decreased the initial hepatic extraction of L-DOPA. When L-DOPA was added alone the initial loss of L-DOPA was 30% at 5 min. At that time the perfusion medium had passed the liver 2.5 times. Between 5 to 60 min. about 5% of the dose was extracted in a single pass through the liver. DHPPA added alone or together with L-DOPA was rapidly converted to L-DOPA, only about half of the DHPPA dose remained unmetabolized in the "plasma" at 2.5 min. The main metabolites in bile of all the compounds tested were conjugates of homovanillinic acid and 3,4-dihydroxyphenylacetic acid.

Animals↗

PubMed1982

Central cardiovascular effects of L-DOPA and clonidine in the lizard, Agama caudospinosa.

The effects of L-DOPA alone and in combination with two inhibitors of 1-aromatic-amino acid decarboxylase (DC), carbidopa and benserazid on the blood pressure (BP) and catecholamine (CA) content in the heart and brain has been investigated in the lizard Agama caudospinosa. The effect of clonidine on BP has also been examined in intact lizards and after spinal cord transection. It is concluded that dopamine (DA) is formed from L-DOPA in brain and heart and that carbidopa reduces the DA formation in the heart but penetrates the blood brain barrier (BBB) poorly, allowing a central decarboxylation of L-DOPA. Benserazid, on the other hand, penetrates the BBB and inhibits the central as well as the peripheral synthesis of DA from L-DOPA. L-DOPA in combination with carbidopa lowers the BP significantly in lizards tilted 45 degrees (head upwards) whereas the supine BP is unaffected. Benserazid pretreatment abolishes the decrease in BP after L-DOPA. L-DOPA alone does not produce any consistent changes in BP. Clonidine lowers BP in intact, tilted animals, while the BP is increased in spinal animals. The results indicate a central mode of action of L-DOPA as well as clonidine in the lizard studied.

Animals↗

PubMed1989

Transfer of DOPA from the sympatho-adrenal system to the pancreas, liver and kidney via the blood circulation.

The concentration of 3,4-dihydroxyphenylalanine (DOPA) was low in the pancreas, liver, kidney, spleen, salivary glands, heart and adrenal glands of untreated mice, but increased following inhibition of DOPA decarboxylase by 3-hydroxybenzylhydrazine. The ratio of the accumulation of DOPA to the concentration of noradrenaline (i.e. the density of sympathetic nerves) was greater in the kidney, liver and, particularly, pancreas than in the other organs studied, suggesting that DOPA occurred outside sympathetic nerves in these organs. The tyrosine hydroxylase inhibitor alpha-methyltyrosine almost completely inhibited the accumulation of DOPA in all organs. The DOPA accumulation was enhanced in all organs by the alpha-adrenoceptor antagonists phentolamine and yohimbine. The results indicate that the DOPA was formed in the sympatho-adrenal system. In the pancreas, liver and kidney, most of the DOPA accumulated might have been formed outside these organs and transferred there via the bloodstream.

Adrenal Glands↗

PubMed2004

Synthesis of 3,4-dihydroxyphenylalanine (DOPA) containing monomers and their co-polymerization with PEG-diacrylate to form hydrogels.

L-3,4-Dihydroxyphenylalanine (DOPA) is an unusual amino acid found in mussel adhesive proteins (MAPs) that is believed to lend adhesive characteristics to these proteins. Most previous efforts to incorporate DOPA into hydrogels have utilized oxidative cross-linking, which is hypothesized to reduce the adhesive properties of DOPA and requires reagents that are harmful to biological tissues. In this paper, we describe the synthesis of N-methacrylated DOPA monomers and their copolymerization with poly(ethylene glycol) diacrylate (PEG-DA) using either ultraviolet (UV) or visible light. The effect of DOPA containing monomers on gelation time, gel conversion and elastic modulus of the photocured hydrogels was investigated. Despite a retarding effect of DOPA on photopolymerization, DOPA was successfully incorporated into hydrogels with elastic moduli suitable for many biomedical applications. The incorporation of DOPA into hydrogels by photopolymerization may lead to new adhesive hydrogels for medical applications.

Dihydroxyphenylalanine↗

PubMed1995

Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson's disease.

The hypothesis that L-DOPA therapy in Parkinson's disease may augment neuronal damage and thus accelerate the progression of the disease remains controversial. In this study, we demonstrate that L-DOPA induces death of catecholaminergic cells in vitro via an active program of apoptosis. Treatment of PC12 cells with clinically applicable concentrations of L-DOPA (25-100 microM) induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation, membrane blebbing, and internucleosomal DNA fragmentation. L-DOPA-induced apoptosis was cell and drug-type specific. Toxicity is an intrinsic property of the drug molecule since it was not suppressed by inhibiting conversion of L-DOPA to dopamine. However, L-DOPA toxicity was inhibited by antioxidants, suggesting that activation of apoptosis is mediated by oxygen radicals. Our finding that L-DOPA-induced cell death in vitro occurs via apoptosis explains the lack of evidence supporting its toxicity in vivo, since apoptotic neurons are rapidly phagocytosed in vivo without causing damage to surrounding tissue. Furthermore, since apoptosis is an active cellular program which can be modulated, we suggest clinical approaches for decreasing L-DOPA toxicity, thus preventing acceleration of neuronal damage in Parkinson's disease.

Animals↗

PubMed1986

Distribution of catecholamines between fetal and maternal compartments during human pregnancy with emphasis on L-dopa and dopamine.

This study was undertaken to determine the differential distribution of catecholamines, in particular L-dihydroxyphenylalanine (L-dopa) and dopamine, between the fetal and maternal compartments during human pregnancy. Amniotic fluid and fetal and maternal blood were obtained from two groups of pregnant women with uncomplicated pregnancies. One group was at 15-20 weeks of gestation and the second group was in labor after 36-41 weeks of gestation. Samples were analyzed for L-dopa, dopamine, norepinephrine, and epinephrine by radioenzymatic assays. L-Dopa constituted about 80% of the total circulating fetal catecholamines, and levels were 2- to 3-fold higher in fetal than maternal plasma. Marked increases in norepinephrine, small rises in epinephrine, but no changes in L-dopa or dopamine concentrations occurred in fetal plasma from mid- to late gestation. Maternal plasma catecholamines did not change. Towards the end of gestation, dopamine in the amniotic fluid increased 15-fold, and norepinephrine increased 5- to 6-fold; L-dopa remained high and unchanged. We conclude that L-dopa is the predominant catecholamine in fetal plasma and amniotic fluid during human pregnancy. No significant changes in its concentrations occur in either compartment between mid- and late gestation. In contrast, dopamine levels, which are 30- to 50-fold lower than those of L-dopa in amniotic fluid during midgestation, show a striking elevation toward the time of labor. Neither the sources nor the possible physiological functions of either L-dopa or dopamine during fetal life are known.

Amniotic Fluid↗

PubMed1993

L-dopa potentiates presynaptic inhibitory alpha 2-adrenoceptor- but not facilitatory angiotensin II receptor-mediated modulation of noradrenaline release from rat hypothalamic slices.

L-dopa is a potentiator for presynaptic beta-adrenoceptors. We studied whether L-dopa potentiates the activities of other presynaptic receptors to modulate the evoked noradrenaline (NA) release in rat hypothalamic slices. UK14304 (0.1-1 microM), a selective alpha 2-agonist, concentration-dependently inhibited NA release. Noneffective 10 pM L-dopa potentiated the UK14304-induced inhibition. This potentiation was selectively antagonized by 1 nM L-dopa methyl ester, a competitive L-dopa antagonist, while yohimbine antagonized both the inhibition by UK14304 alone and its potentiation by L-dopa. However, 10 pM L-dopa produced no effect on angiotensin II (0.1-1 nM)-induced facilitation. L-dopa potentiates activities of presynaptic beta- and alpha 2-adrenoceptors but not those of angiotensin II receptors on rat hypothalamic NA neurons.

Adrenergic alpha-Agonists↗

PubMed2006

Effects of subchronic treatment with selegiline on L-DOPA-induced increase in extracellular dopamine level in rat striatum.

Selegiline is used an adjunct to L-DOPA therapy. We investigated extracellular striatal dopamine (DA) level in awake rats treated with L-DOPA and/or selegiline using a microdialysis method. Rats given 10 mg/kg, i.p. per day selegiline for 7 days were administered with a single dose of 100 mg/kg, i.p. L-DOPA 0 (3 h), 1, 3, 7, 14, 21, or 28 days after the last selegiline treatment. Carbidopa was administered 0.5 h before L-DOPA administration. The significant increase in basal DA level before L-DOPA treatment persisted until 1 day after the last selegiline treatment, and the significant decrease in basal DOPAC level persisted for more than 28 days. Thus, selegiline affected DA catabolism for more than 28 days. Total monoamine oxidase (MAO) and MAO-B activities at day 0 decreased by 22% and 5.7%, respectively. The significant enhancement of L-DOPA-induced increase in DA level was observed until 3 days after the last selegiline treatment. Next, the effects of reducing L-DOPA dose by 25% were examined 3 h after the last selegiline treatment. A dose-dependent decrease in DA level was observed, indicating that DA level in selegiline-treated rats can be controlled by L-DOPA dose.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1975

[A low response of pituitary growth hormone secretion in the patient with diabetes mellitus after intravenous administration of L-dopa (author's transl)].

Recently, L-dopa has been known as one of drugs to stimulate the secretion of growth hormone from the pituitary gland through dopamine, which is a metabolic of L-dopa, without any changes of serum insulin levels, blood sugar values, fatty acids and amino acids concentrations in the serum of human being. The present study was thus designed to assess the effect of L-dopa on the pituitary gland to secrete the growth hormone in the normal subject and the study was further extended to compare the response of the pituitary secretion of the growth hormone following the administration of L-dopa between in the patient with diabetes mellitus and in the normal subject. In the present experiment, 5 normal subjects and 11 diabetes mellitus without obesity were employed and they received a 30 min infusion of 200 mg L-dopa dissolved in 200 ml physiological saline. In normal subjects, serum growth hormone concentration measured by radio-immunoassay was started to increase within 10 min after L-dopa administration and maximum value of serum growth hormone was obtained 60 min after the drug, mean values of it, 30 ng/ml of serum. Then it was declined sharply upto the values of 2-3 ng/ml. In the patients with diabetes mellitus, on the other hand, maximum value of serum concentration of the growth hormone was only approximately 5 ng/ml of serum obtained between 45 and 75 min after the administration of L-dopa. No changes in the serum concentration of IRI (Immunoreactive insulin) and of blood sugar values were observed by the infusion of L-dopa in both normal subjects and diabetes mellitus. From the above mentioned facts, it was concluded that the ability of pituitary gland to secrete the growth hormone was considerably impaired in diabetics when it was compared with normal subjects.

Adult↗

PubMed1987

[Effect of oral administration of L-dopa on the plasma levels of growth hormone-releasing hormone (GHRH) in normal subjects and patients with various endocrine and metabolic diseases].

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.

Adolescent↗

PubMed1989

Plasma dopa and feeding.

Dopa is a normal constituent of plasma in man and experimental animals. Dopa concentrations in plasma have been used to reflect the activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines. However, it is not known to what extent plasma dopa is affected by feeding, since several foods contain dopa or tyrosine, the immediate precursor of dopa. In this study dopa and its major metabolites (3-O-methyldopa and free and conjugated catecholamines) were measured in plasma of dogs during 5 hr after feeding. Plasma dopa did not change significantly after feeding. This finding increases the value of plasma dopa as an index of tyrosine hydroxylase activity. Plasma norepinephrine decreased, and conjugated dopamine increased, after feeding; the other analytes did not change significantly.

Animal Feed↗

PubMed2002

Effect of bicalutamide therapy on prolactin response to L-dopa in metastatic prostate cancer patients.

OBJECTIVES: The secretion of prolactin (PRL), which is a growth factor for prostate cancer cell proliferation, has been proven to present profound alterations in advanced prostate cancer patients, consisting of abnormally elevated baseline levels and paradoxical response to L-dopa. Moreover, the efficacy of standard therapies for prostate cancer may be mediated at least in part by changes in PRL secretion. The present study was carried out to analyze the effects of the new antiandrogen agent bicalutamide on basal levels of PRL and on its response to L-dopa in metastatic prostate cancer patients. MATERIAL & METHODS: The study included 10 metastatic prostate cancer patients. They were treated with bicalutamide at a dose of 50 mg/day orally. They were investigated with L-dopa test before therapy and after one month of treatment. L-dopa was given orally at 500 mg, by collecting blood samples before and at 60, 120 and 180 minutes after L-dopa administration. Serum levels of PRL were measured by the RIA method. RESULTS: Abnormally basal levels of PRL were seen in 4/10 (40%) patients. Mean PRL basal levels decreased after bicalutamide therapy, without, however, significant differences. Before therapy, a paradoxical increase in PRL levels after L-dopa occurred in 4 patients, 3 of them showed basal concentrations of PRL within the normal range. Moreover, bicalutamide therapy significantly reduced PRL increase in response to L-dopa. CONCLUSIONS: This study would suggest that the measurement of the only basal levels is not sufficient to define as normal the secretion of PRL in advanced prostate cancer, because of the possible existence of altered response to the dynamic tests for PRL secretion. Moreover, the study shows that the antitumor therapy with the new anti-androgen bicalutamide may reduce PRL secretion and improve its paradoxical secretion in response to L.-Dopa. Further studies will be required to better define the possible prognostic impact of changes in PRL secretion on the efficacy of treatments for metastatic prostate cancer.

Aged↗

PubMed1976

Centrally mediated increased reflex vagal bradycardia after L-dopa in monoamine oxidase-inhibited anesthetized dogs.

In monoamine oxidase-inhibited dogs whose peripheral dopa decarboxylase was inhibited with MK-486, L-dopa (K mg/kg i.v.) caused significant hypotension and bradycardia. In addition, reflex bradycardia but not pressor responses to norepinephrine were markedly enhanced by the drug. Similar results were obtained after intracerebroventricular administration of L-dopa (0.5 mg/kg) in monoamine oxidase-inhibited dogs not receiving MK-486. Proparnolol prevented the bradycardia caused by L-dopa but was without effect on the reflex facilitation. Both atropine and phentolamine had no effect on L-dopa bradycardia but prevented the facilitatory effect on reflexes. Inhibition of both peripheral and central dopa decarboxylase with Ro 4-4602 prevented all the effects of L-dopa. Infusions of dopamine which had obvious cardiovascular effects had no effect on reflex responses to norepinephrine. It is concluded that L-dopa, after decarboxylation, causes a centrally mediated enhancement of reflex vagal bradycardia. Pharmacological analysis of this enhancement suggests that this effect appears to be a result of central alpha receptor stimulation.

Animals↗

PubMed2003

Characterization of a new amino acid transport system in human epidermal Langerhans cells: the L-dopa influx/efflux cycle.

Various aspects concerning the L-dopa uptake mechanism into human epidermal Langerhans cells (LC) and the energy metabolism of epidermis have been examined. The study is based on the discovery of a new amino acid transport system in human epidermal LC. The amino acid transport system has been characterised. This system is stereospecific and is unique for L-dopa and LC as it does not share any characteristics with other described transport systems of other amino acids in other cell types. The uptake assay is based on the Falck/Hillarp histofluorescence method, which enables studying uptake in individual LC in situ in their microenvironment. For the first time, it is shown that the human epidermis is capable of an aerobic lactate production, which is a strange phenomenon, as this means that epidermal cells, despite the formal presence of mitochondria, nevertheless produce lactate in excess. This probably depends on a disturbed Pasteur effect. The same phenomenon is found under normal conditions in smooth muscle cells, but has not been described in other human cells. Also, for the first time, it is shown that the human epidermis has a lower energy charge value than other body cells except for, again, smooth muscle cells. The increased lactate production in epidermis, which can be inhibited by iodoacetate, implies an increased intracellular proton production. The energetics of the L-dopa transport into the LC is probably a counter-transport (antiport) of protons due to the aerobic production of lactate. It is proved that L-dopa can be dislocated out of the LC by certain amino acids on the outside of the cell, some acting in a trans-stimulatory fashion and others probably by exchanging with intracellular L-dopa, hereby getting "useful" amino acids into the cell instead. This, now extracellular L-dopa, can then begin a new in- and out-transport cycle. For further characterisation of the L-dopa transport system, experiments have been carried out with an H+,K+-ATPase-inhibitor (omeprazole and a number of its analogues). Most of these are inhibitory of the L-dopa transport into LC. This is most probably not caused by an effect on a thiol group essential for this transport, but the actual mechanism is not known.

Amino Acids↗

PubMed1992

Delayed L-phenylalanine infusion allows for simultaneous kinetic analysis and improved evaluation of specific-to-nonspecific fluorine-18-dopa uptake in brain.

The accumulation of 3-O-methyl-6-[18F]fluoro-L-DOPA (18F-30M-DOPA) in the brain from the circulation is responsible for most of the nonspecific background during 18F-DOPA positron emission tomography scanning. To increase the sensitivity of 18F-DOPA for imaging presynaptic dopamine systems, we took advantage of 18F-30M-DOPA's rapid clearance from the brain (T1/2 approximately 15-20 min). The infusion of the unlabeled amino acid L-phenylalanine, starting 75 min after 18F-DOPA administration, prevents 18F-30M-DOPA entrance into the brain through competition at the large amino acid transport system of the blood brain barrier. This method produces high specific-to-nonspecific contrast images of 18F accumulation beginning 15-30 min after onset of amino acid infusion and better sensitivity to small changes in 18F-DOPA uptake while still allowing for kinetic analysis of the data in the early time points. Kinetic and anatomical data were found to be strongly correlated.

Animals↗

PubMed1989

Dopa in plasma increases during acute exercise and after exercise training.

Plasma dihydroxyphenylalanine (dopa) has been shown to originate in sympathetic neurons, and it has been suggested that plasma level reflects activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines. In this study, we measured the effects of acute exercise and exercise training on the levels of dopa and catecholamines in the plasma of healthy, older individuals. Venous blood was drawn from 19 men, from 52 to 75 years of age, at rest, at a standard submaximal work load, at peak exercise, and 3 minutes after exercise on a cycle ergometer. Ten of 12 men then completed 12 to 16 weeks of supervised training, and seven continued normal activity. All 17 men were then retested. The seven control subjects subsequently underwent exercise training as above and were retested again. Levels of dopa and catecholamines in plasma samples were measured by high-performance liquid chromatography with electrochemical detection. Dopa levels at rest were considerably higher than free dopamine, epinephrine, and norepinephrine. During short-term exercise, levels of dopa and catecholamines increased. The absolute increase in dopa was greater than the increase in epinephrine or dopamine but was not greater than that in norepinephrine. After the training period, basal dopa levels increased significantly and correlated with the increase in peak oxygen uptake. There was no change in basal conjugated norepinephrine or dopamine levels with exercise or training, but the level of conjugated epinephrine decreased slightly. No changes occurred in levels of dopa or catecholamines in the untrained group. Free dopamine, norepinephrine, and epinephrine levels at peak exercise were increased after exercise training.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Specimen Collection↗

PubMed1989

NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys.

Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 4 1/2 h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 4 1/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by approximately 40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Sensitivity of human melanoma cells to L-dopa and DL-buthionine (S,R)-sulfoximine.

Four of seven human melanoma cell lines were sensitive to killing by L-dopa (D37 1.0-4.7 microM) compared with fibroblasts, Hela, and three ovarian tumor cell lines (D37 12-59 microM). All seven melanoma lines, however, were sensitive to DL-buthionine(S,R)sulfoximine (BSO) (D37 0.73-8.5 microM) compared with the nonmelanoma cells (D37 25-68 microM). The melanoma line most sensitive to BSO (MM418) was highly melanized, proliferated slowly and was resistant to other agents [dopa, 5-(3-methyl-1-triazeno)5-imidazole-4-carboxamide, melphalan, methotrexate, hydroxyurea, etoposide, Adriamycin]. In most cell lines, L-dopa and BSO blocked cell proliferation in all phases of the cell cycle. Cellular sensitivity to dopa or BSO did not correlate with levels of total soluble SH, glutathione (GSH), GSH reductase, GSH peroxidase or GSH transferase, or with the extent of GSH depletion induced by the drug. No GSH transferase activity could be detected in the dopa-resistant HeLa line, indicating that detoxification of quinones is not an important mechanism of resistance. Within the group of melanoma cell lines, sensitivity to dopa correlated with decreased level of gamma-glutamyl transpeptidase (r = 0.81). However, the gamma-glutamyl transpeptidase inhibitor azaserine was less effective than BSO in enhancing the toxicity of dopa. It can be inferred that (a) there is no simple relationship between GSH metabolism and sensitivity to dopa or BSO in human melanoma cells, and (b) BSO may be an effective agent for melanoma.

Buthionine Sulfoximine↗