Disease relevance of dihydroxyphenylalanine

• Possible enzymatic defects contributing to CRF-induced increases of DOPA and DA sulfates and their potential role in perpetuating renal failure via glomerular hypertension are discussed [1].
• Other newer specific modalities that have been used for evaluating pheochromocytomas include positron emission tomography (PET) with [18F]-F-fluorodopamine (F-DA) and [18F]-F-dihydroxyphenylalanine (DOPA) [2].
• Baseline dihydroxyphenylalanine (DOPA) and dopamine (DA), their respective sulfates as well as oral DOPA administration-induced changes were compared in age- and blood pressure-matched hypertensive patients without and with moderate chronic renal failure (CRF) and control subjects [1].

Psychiatry related information on dihydroxyphenylalanine

• Using two in vivo measures of presynaptic DA receptor sensitivity, the antagonism of spontaneous locomotor activity and the antagonism of dihydroxyphenylalanine (DOPA) accumulation by apomorphine (APO), individually housed mice showed greater activity counts and higher DOPA accumulations than group housed mice [3].

High impact information on dihydroxyphenylalanine

• The rank order of the potencies of enkephalins and their analogs for inhibition of DOPA accumulation in the median eminence was similar to that of their binding capacities for opioid receptors [4].
• The inhibitory action of ENKamide was more pronounced in hypothalamic slices from haloperidol-treated rats in which basal DOPA accumulation in the median eminence was stimulated by increased PRL secretion [4].
• DOPA also depressed extracellular field potentials evoked by group II afferents in the intermediate zone and in the ventral horn (at the location of the interneurones) but hardly affected those in the dorsal horn [5].
• Concentrations of the neurotransmitter dopamine (DA), and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), as well as D-2 dopamine receptor binding, 3,4-dihydroxyphenylalanine (DOPA) decarboxylase activity, and vitamin B6 levels were measured in the corpus striatum of progeny at 7, 14, and 18 days after birth [6].
• The in vivo effects on dopamine (DA) metabolism in limbic (accumbens) and extrapyramidal (striatum) regions of rat brain were evaluated by measuring the accumulation of L-dihydroxyphenylalanine (DOPA) after inhibiting decarboxylation alone ("open-loop" model) or with added gamma-butyrolactone (GBL, autoreceptor model) [7].

Biological context of dihydroxyphenylalanine

• The first dose of dexamethasone increased about 100% diuresis and natriuresis, increased urinary DOPA and renal plasma flow, and did not affect urinary dopamine or the other parameters evaluated [8].
• The proposed D3-selective ligand (+/-)-7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) inhibited tyrosine hydroxylase in vitro (IC50 = 0.6-0.7 microM) and dihydroxyphenylalanine (DOPA) accumulation in vivo (ID50 = 4.8-6.4 mg/kg) in two autoreceptor models in extrapyramidal and limbic tissue in rat forebrain, without consistent regional selectivity [9].
• MK-801 increased the rate of tyrosine hydroxylation (measured as the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of DOPA decarboxylase) in the striatum with no change in DOPA formation in the limbic forebrain [10].

Anatomical context of dihydroxyphenylalanine

• The increased synthesis of DA in the nucleus accumbens septi [demonstrated by increased accumulation of dihydroxyphenylalanine (DOPA)] was abolished by the intravenous administration of d-amphetamine, in patterns mimicking those of animals trained in self-administration [11].
• Depending on the dose, d-AMP increased or had no effect on the accumulation of DOPA in the striatum but consistently decreased it in the substantia nigra [12].
• In desipramine-treated rats (10 mg/kg, 21 days), but not in fluoxetine-treated ones (3 mg/kg, 14 days), the effect of clonidine was attenuated in cortex (12% and 18%) and only for dopa synthesis in hippocampus (31%) [13].
• In morphine-dependent rats (tolerant state), the inhibitory effects of clonidine on the synthesis of DOPA/NA (hippocampus, hypothalamus) and DOPA/DA (striatum) also were potentiated (35%-55%) [14].
• DOPA accumulation was also measured in the frontal cortex, olfactory tubercle, and caudate nucleus of the same rats for comparative purposes [15].

Associations of dihydroxyphenylalanine with other chemical compounds

• The amount of dopamine released during 1 h into hypophysial portal blood of vehicle-treated rats represented 18% of the amount of DOPA that accumulated in 1 h in the median eminence of rats treated with NSD 1015 [16].
• SKF 38393 (5-20 mg/kg) and CY 208-243 (5-20 mg/kg) alone did not alter the accumulation of DOPA in the median eminence of male rats [17].
• Mild-footshock stress increased frontal cortex DOPA accumulation, as well as DA and DOPAC, without changing the concentration of these substances in the corpus striatum [18].
• Using liquid chromatography and electrochemical detection (LCEC), we have measured the accumulation of 3,4-dihydroxyphenylalanine (DOPA) (after L-aromatic amino acid decarboxylase inhibition), dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the frontal cortex and in the corpus striatum of the rat [18].
• However, the clozapine-induced increase in DOPA accumulation in the median eminence was not significantly altered by treatment with amfonelic acid [19].

Gene context of dihydroxyphenylalanine

• The stimulatory effect of PACAP (0.1 microgram) on median eminence DOPA could also be blocked by coadministration of a PACAP antagonist, PACAP6-38 (in 10 to 100 x higher doses) [20].
• We measured the accumulation of L-3,4-dihydroxyphenylalanine (DOPA) after the inhibition of aromatic L-amino acid decarboxylase with 3-hydroxylbenzylhydrazine (NSD-1015, 100 mg kg(-1)) as an in vivo index of dopamine synthesis [15].
• The present investigation has revealed that melanin synthesized in vitro from dopa formed a complex with purified mushroom tyrosinase [21].
• When dizocilpine was given to animals treated with NSD 1015, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylase and monoamine oxidase, there was an increase in levels of DOPA and 3-methoxytyramine (3-MT) [22].
• CONCLUSION: The relationship between HVR and the reciprocal DA and DOPA values seen in both groups is associated with age, producing decreased DA receptor sensitivity and enhanced DA reuptake during adaptation to high altitude [23].

Analytical, diagnostic and therapeutic context of dihydroxyphenylalanine

• Ovariectomy produced a time-dependent decrease in the accumulation of DOPA and the concentrations of DOPAC in the median eminence and prolactin in plasma with maximal effects occurring by 7 days [24].
• 2. Denervation did not change D production or DOPA consumption.(ABSTRACT TRUNCATED AT 250 WORDS)[25]

References