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S Tanganelli

Publications and source records attributed to S Tanganelli.

At least 55 records · Page 3Linked to original sources
PubMed1994

Facilitation of GABA release by neurotensin is associated with a reduction of dopamine release in rat nucleus accumbens.

The main aim of the present study was to investigate the effects of local perfusion with the tridecapeptide neurotensin on extracellular GABA and dopamine levels in the nucleus accumbens of the halothane-anaesthetized rat, using in vivo microdialysis. In an initial set of characterization studies we examined the Na+ dependence of neurotransmitter release by local perfusion with ouabain, veratridine and tetrodotoxin. Local perfusion with the Na+ ATPase inhibitor ouabain (10 microM) or the Na+ channel agonist veratridine (20 microM) perfused into the nucleus accumbens increased both extracellular GABA and dopamine levels. The Na+ channel antagonist tetrodotoxin (1 microM) consistently decreased (24% of basal) dopamine levels, while even at 10 microM it did not affect GABA. However, tetrodotoxin (10 microM) abolished the veratridine-induced increase in both GABA and dopamine, demonstrating that Na(+)-dependent neuronal activity is involved in this release mechanism. In a second set of experiments a hypothesis for a functional link between neurotensin, dopamine and GABA in the medial nucleus accumbens was tested. Towards this aim, the effects of local perfusion with a high 1 microM concentration of neurotensin into the nucleus accumbens increased both GABA (210% of basal value) and dopamine (145% of basal) release. However, a low (10 nM) concentration of neurotensin again increased GABA release (160% of basal), but decreased that of dopamine (75% of basal value). Furthermore, the local perfusion with the GABAA receptor antagonist bicuculline abolished the neurotensin (10 nM) induced inhibition of dopamine release without affecting the increase in GABA release. These findings suggest that neurotensin modulates both GABA and dopamine neurotransmission in the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Influence of the herbicide Linuron on growth rate and gap-junctional intercellular communication of cultured endothelial cells.

On the basis of in vivo toxicological long-term tests performed on rodents, the herbicide Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] has been classified by the U.S. Environmental Protection Agency (EPA) (1988) as a class C carcinogen (possibly carcinogenic to humans). However, when Linuron was analyzed for genotoxicity, negative results were obtained. An epigenetic, tumor-promoting potential was hence suspected to be responsible for the oncogenic activity of the molecule. In the absence of in vivo data concerning the tumor-promoting activity of the herbicide and being well established that tumor promoters interfere with the cell growth rate and gap-junctional permeability, the effects of technical grade Linuron and of its trade formulation (Linuron 50) on these parameters were investigated. This is especially important in the case of the formulated preparation for a correct estimate of the health hazard to humans. Cytotoxicity and gap-junctional intercellular communication (GJIC) assays were performed on the endothelial cell line F-BAE GM 7373, an in vitro cell system known to be responsive to the biological effects of tumor promoters. A time- and dose-related cytotoxic effect was found for both Linuron and Linuron 50, the latter being the far more cytotoxic of the two. However, when tested at noncytotoxic concentrations over a period of 48 h, neither Linuron nor Linuron 50 altered the capacity of F-BAE GM 7373 cells to intercommunicate. On the basis of the results obtained, the possibility that Linuron and Linuron 50 are endowed with tumor-promoting activity is discussed. In vivo studies on tumor-promoting and genotoxic activity are in progress to complement the information available on the toxicological properties of Linuron and its trade preparation.

Cell Communication↗
PubMed1993

Noradrenergic modulation of gamma-aminobutyric acid outflow from the human cerebral cortex.

The noradrenergic modulation of endogenous gamma-aminobutyric acid (GABA) outflow from slices and synaptosomes prepared from human cerebral cortex biopsies has been studied. GABA outflow was responsive to depolarizing stimuli such as ouabain and high potassium. Basal GABA outflow in slices, but not in synaptosomes, appeared to be largely dependent upon neuronal activity, being prevented by tetrodotoxin (TTX). 10 mM K(+)-evoked outflow in synaptosomes also proved to be TTX sensitive. Norepinephrine (NE) concentration dependently increased basal GABA outflow both in slices and synaptosomes. This effect was alpha 1-adrenoreceptor-mediated because it was prevented by a selective antagonist of the alpha 1-adrenoreceptor class (prazosin) but not by the alpha 2 antagonist idazoxan. However, an alpha 2-mediated inhibitory modulation was also present in the preparations used, since (1) in slices, NE significantly inhibited GABA outflow in the presence of prazosin; (2) in synaptosomes, NE significantly inhibited 10 mM K(+)-evoked outflow in the presence of prazosin. Both of these effects were prevented by idazoxan. No beta-adrenoreceptor modulation could be demonstrated. A comparison between species was also conducted. The response to ouabain and to TTX proved similar in human, rat and guinea-pig cerebral cortex. In the most simple tissue preparation used (synaptosomes), a close similarity between the three species could be observed. In all species, NE stimulated basal GABA outflow, an effect prevented by prazosin. This suggests a predominant alpha 1-adrenoreceptor-mediated stimulatory effect. In a more complex preparation (slices), differences between species could be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1993

Neurotensin and cholecystokinin octapeptide control synergistically dopamine release and dopamine D2 receptor affinity in rat neostriatum.

Combined perfusion of the neostriatum with 1 nM of cholecystokinin octapeptide (CCK-8) and 0.01, 0.1 or 1 nM of neurotensin was done in the halothane-anesthetized rat after systemic apomorphine treatment (0.05 mg/kg, s.c.). Neurotensin (1 nM) plus CCK-8 (1 nM) effectively counteracted the apomorphine-induced inhibition of neostriatal perfusate levels of dopamine (DA). With a constant concentration of CCK-8 (1 nM), the apomorphine-induced inhibition of DA release was counteracted dose relatedly by neurotensin in concentrations of 0.01, 0.1 and 1 nM. The results of binding experiments demonstrated that threshold concentrations of CCK-8 and neurotensin significantly increased the KD values of the high-affinity D2 receptors without significant alterations in the low-affinity D2 receptors or in the proportion of D2 receptors in the high-affinity state. Thus, neurotensin and CCK receptors may regulate synergistically, via intramembrane interactions with the D2 receptors, the binding characteristics and the signal transduction of D2 autoreceptors in the neostriatum. The combined presence of very low concentrations of CCK-8 and neurotensin in the extracellular fluid may be sufficient to regulate D2 receptor transduction, underlining the important role of these peptide receptor interactions with the D2 receptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Evidence for a preventive action of the vigilance-promoting drug modafinil against striatal ischemic injury induced by endothelin-1 in the rat.

We have studied the ability of the vigilance-promoting drug modafinil to counteract the ischemic lesion produced by a unilateral microinjection of endothelin-1 (ET-1) in the neostriatum of the rat using a combined morphometrical, biochemical, cardiovascular and behavioral analysis. ET-1 was injected unilaterally into the neostriatum. The ET-1-induced lesion volume, which was determined by a computer-assisted morphometrical analysis, was reduced by the 7-day modafinil treatment (10, 30, and 100 mg/kg i.p.) in a dose-related way. Modafinil also produced a dose-related counteraction of the ET-1-induced increase of perfusate lactate levels, as determined by intrastriatal microdialysis without affecting the ET-1 induced reduction of striatal blood flow, as determined by laser-Doppler flowmetry. The ipsilateral rotational behavior induced by apomorphine in the ET-1-lesioned rats was reduced dose-dependently by modafinil treatment. Thus, morphological, neurochemical, and behavioral evidence that the putative ischemic striatal injury induced by microinjection of ET-1 in the rat neostriatum is counteracted in a dose-dependent way by modafinil treatment has been obtained. The mechanism does not appear to involve an increase in striatal blood flow. It is instead speculated that its powerful preventive action in striatal ischemic injury may be related to a reduced anaerobic metabolism.

Amphetamine↗
PubMed1992

Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum.

The major mechanism underlying the neuroleptic action of the tridecapeptide neurotensin (NT) appears to be an interaction with dopamine receptor mechanisms based on biochemical binding and behavioral experiments. In vivo microdialysis was used in conscious rats to investigate the effects of local perfusion with NT on the sensitivity of striatal dopamine D1 and D2 receptors for their selective agonists by monitoring extracellular dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, and gamma-aminobutyric acid levels in the awake unrestrained male rat. Perfusion with NT (10 nM) counteracted the inhibitory effects of the dopamine D2 agonist pergolide (500 nM) on extracellular levels of dopamine and gamma-aminobutyric acid. In contrast, NT (10 mM) significantly enhanced the reduction of extracellular striatal levels of dopamine after perfusion with the D1 agonist SKF 38393 (5 microM), and this combined treatment also resulted in a significant increase in the extracellular striatal levels of gamma-aminobutyric acid. These results provide in vivo evidence that NT regulates central dopamine transmission by reducing pre-and postsynaptic dopamine D2 and enhancing D1 receptor sensitivity possibly through an antagonistic NT receptor-D2 receptor interaction. This heteroregulation has the potential to substantially increase the plasticity within the dopamine synapse.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

The effects of neurotensin on GABA and acetylcholine release in the dorsal striatum of the rat: an in vivo microdialysis study.

The effects of local perfusion with the tridecapeptide neurotensin (NT) on endogenous gamma-aminobutyric acid (GABA), acetylcholine (ACh) and choline release in the dorsal neostriatum were monitored using in vivo microdialysis in the halothane anaesthetized rat. The results show that NT (10 and 1000 nM) differentially regulates striatal GABA release without significantly influencing the release of either striatal ACh or choline. NT increased striatal GABA release both in the absence and presence of the ACh esterase inhibitor neostigmine (neo; 10 microM) in the perfusion medium. However, both basal GABA levels and responsitivity to NT were elevated in the presence of neo. The NT induced increase in striatal GABA release was reversed by the addition of tetrodotoxin (TTX; 1 micron) to the perfusion medium. These data suggest that (1) NT may play a role in modulating GABAergic neurotransmission in the dorsal neostriatum and (2) that the increase in GABA release may occur independently of an increase in the cholinergic component in the dorsal neostriatum, possibly via high affinity NT receptors located on striatal GABAergic neurons.

Acetylcholine↗
PubMed1992

Inhibitory effects of the psychoactive drug modafinil on gamma-aminobutyric acid outflow from the cerebral cortex of the awake freely moving guinea-pig. Possible involvement of 5-hydroxytryptamine mechanisms.

The effects of modafinil on acetylcholine and GABA outflow from the cerebral cortex of awake freely moving guinea pigs provided with an epidural cup were studied. In the dose range of 3-30 mg/kg s.c. modafinil produced a dose dependent significant inhibition of GABA outflow without influencing cortical acetylcholine release. Methysergide (2 mg/kg, i.p.) and ketanserin (0.5 mg/kg, i.p.) but not prazosin (0.14 mg/kg, i.p.) counteracted the inhibitory action of modafinil on cortical GABA outflow. Modafinil both acutely and chronically in the same dose range increased striatal 5-HIAA levels and 5-HT utilization in the rat (acute) and mouse (chronic). The action on cortical GABA release may be dependent on activity at 5-HT2 receptors, since the action of modafinil in this respect is blocked by the non-selective 5-HT antagonist methysergide and the 5-HT2 antagonist ketanserin. The involvement of 5-HT mechanisms in the inhibitory action of modafinil on cortical GABA release is also suggested by the findings that 5-HT metabolism may become increased by modafinil at least in the striatum. The reduction of cortical GABA outflow via 5-HT2 receptors by modafinil is probably related to some of its actions on the central nervous system including behavioural effects.

Acetylcholine↗
PubMed1992

Evidence for a protective action of the vigilance promoting drug modafinil on the MPTP-induced degeneration of the nigrostriatal dopamine neurons in the black mouse: an immunocytochemical and biochemical analysis.

Based on the observations that the psychostimulant drug amphetamine in combination with physiotherapy can promote recovery of brain function after brain injury, we have studied the ability of the vigilance promoting drug Modafinil to counteract 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-(MPTP)-induced degeneration of the nigrostriatal dopamine (DA) neurons of the black mouse. MPTP was given s.c. in a dose of 40 mg/kg and the mice were sacrificed 2 weeks later. The effects of acute and chronic treatment with Modafinil were studied on MPTP-induced DA neurotoxicity. The substantia nigra and neostriatum were taken to both biochemical and histochemical analysis of presynaptic parameters of the nigrostriatal DA neurons, the latter in combination with image analysis. In separate experiments in rats in vivo tests for DA uptake blocking activity were made using intrastriatal microdialysis to study superfusate levels of DA and its metabolites and the 4-alpha-dimethylmetatyramine (H77/77) model to test for a possible ability of Modafinil to protect against H77/77-induced depletion of forebrain DA stores. Chronic treatment with Modafinil in doses of 10 to 100 mg/kg counteracted the MPTP-induced disappearance of nigral TH IR nerve cell body profiles and neostriatal TH IR nerve terminal profiles as evaluated after 2 weeks with image analysis. Chronic treatment with Modafinil (10-100 mg/kg) also dose-dependently counteracted the MPTP-induced disappearance of striatal DA uptake binding sites as evaluated at the same time interval. Also in the dose range 10-100 mg/kg Modafinil counteracts the MPTP-induced depletion of DA stores both in the neostriatum and the substantia nigra. In the acute experiments Modafinil (30 mg/kg) protected against the MPTP-induced depletion of striatal DA, dihydrophenylacetic acid (DOPAC) and homovanillic acid (HVA) levels both when given 15 min before, at the same time and 3 h following the MPTP injection. In the substantia nigra, however, these protective actions of Modafinil were only observed when the drug was coadministered with MPTP. Experiments with microdialysis in intact rats failed to demonstrate any increases of superfusate DA levels in neostriatum with 30 mg/kg of Modafinil. Modafinil in high doses of 2 x 50 mg/kg, however, significantly counteracted the H77/77 induced DA depletion of striatal DA stores. Thus, morphological and biochemical evidence has been obtained that Modafinil in the dose range 10-100 mg/kg protects against MPTP-induced degeneration of the nigrostriatal DA neurons of the black mouse.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Changes in gamma-aminobutyric acid release induced by topical administration of drugs affecting its metabolism and receptors: studies in freely moving guinea pigs with epidural cups.

The effect of local application of drugs affecting gamma-aminobutyric acid metabolism and receptors on cortical aminoacid release has been investigated in freely-moving guinea pigs equipped with epidural cups. Topical treatment with gamma-aminobutyric acid reuptake and/or metabolism inhibitors (alone and in combination) produced a slow and progressive increase in cortical aminoacid release. The inhibition of gamma-aminobutyric acid-transaminase with ethanolamino-O-sulphate seemed to be a suitable procedure for enhancing the gamma-aminobutyric acid efflux without interfering with its autoreceptor-mediated negative feedback, tested with the gamma-aminobutyric acid agonist (+/-)baclofen and antagonist phaclofen. A substantial part of the gamma-aminobutyric acid outflowing from the cortex was of neuronal origin since tetrodotoxin halved the basal efflux in the presence of gamma-aminobutyric acid reuptake and/or metabolism inhibitors. These results, considered together, indicate that the epidural cup technique may be a useful approach to study changes in cortical gamma-aminobutyric acid release induced by drugs acting on gabaergic transmission and directly applied on the surface of the cortex.

4-Aminobutyrate Transaminase↗
PubMed1992

Intramembrane interactions between neurotensin receptors and dopamine D2 receptors as a major mechanism for the neuroleptic-like action of neurotensin.

Evidence has been presented that behavioral actions of NT, inducing its neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane receptor-receptor interactions in the basal ganglia, unrelated to the coexistence phenomenon, leading to reduced affinity and transduction of the D2 agonist binding site. By reducing selectively D2 receptor transduction at the pre- and postsynaptic level, the NT receptor appears capable of switching the DA synapses towards a D1 receptor-mediated transduction, illustrating how receptor-receptor interactions can increase the functional plasticity of central synapses (FIG. 12).

Animals↗
PubMed1991

Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs.

The effects of excitatory amino acid antagonists on increased cortical acetylcholine release and behavioral hyperactivity induced by naloxone in morphine tolerant guinea pigs and mice were studied. The results show that the N-methyl-D-aspartic acid (NMDA) antagonist MK-801 (0.1-1 mg/kg, i.p.) injected 30 min before naloxone (3 mg/kg, s.c.) dose-dependently prevented the neurochemical and behavioral signs of morphine withdrawal in guinea pigs and mice. The non-selective antagonist glutamic acid diethylester only at 100 mg/kg i.p. reduced the naloxone-induced increase of cortical acetylcholine release without affecting the behavioral changes. These findings indicate that the activation of excitatory amino acid receptors, mainly the NMDA receptors, plays a relevant role in the expression of opiate abstinence.

Acetylcholine↗
PubMed1991

Effect of acute and subchronic nicotine treatment on cortical efflux of [3H]-D-aspartate and endogenous GABA in freely moving guinea-pigs.

1. The [3H]-D-aspartate preloading of the parietal cortex of freely moving guinea-pigs equipped with epidural cups makes it possible to investigate drug effects on the efflux of this radiolabel, assumed as a marker of the glutamatergic structures underlying the cup. In the same model, the efflux of [3H]-gamma-aminobutyric acid ([3H]-GABA) and endogenous GABA can be measured. 2. Nicotine, 0.9-3.6 mg kg-1, s.c., or 3-5 micrograms, i.c.v., increased the efflux of [3H]-D-aspartate but reduced that of GABA. 3. These effects were mediated through mecamylamine-sensitive receptors but the ganglionic blocking agent was devoid of any primary activity. 4. The inhibition of GABA efflux induced by nicotine 3.6 mg kg-1, s.c., was abolished by methysergide 2 mg kg-1, i.p. and was reduced by naloxone 3 mg kg-1, i.p. pretreatment, suggesting the involvement of tryptaminergic and opioid systems. In contrast, muscarinic and catecholamine antagonists were ineffective. 5. Chronic treatment with nicotine (3.6 mg kg-1, twice daily for 16 days) reduced the facilitatory effect of [3H]-D-aspartate and abolished the inhibition of endogenous GABA efflux. 6. A slight increase in the number of nicotinic binding sites (by use of [3H]-nicotine as ligand) was found in the neocortex of chronically treated guinea-pigs. 7. The higher degree of tolerance to chronic nicotine treatment shown by GABA as compared with [3H]-D-aspartate efflux suggests that adaptative changes of the inhibitory neuronal pools prevail. This may contribute to the reinforcing and addictive properties of nicotine.

Acetylcholine↗
PubMed1991

Alpha-2 adrenoreceptor-mediated decrease in gamma-aminobutyric acid outflow in cortical slices and synaptosomes during morphine tolerance.

Morphine tolerance has proven to be accompanied by alterations in the efficiency of many neuronal signals, as well as by an inversion of the noradrenergic signal response of cortical acetylcholine terminals and gamma-aminobutyric acid (GABA) neurons in vivo (decreased acetylcholine and increased GABA release in normal animals, vice versa in tolerant). The latter observation may be relevant in interpreting morphine withdrawal, because the noradrenergic neuron firing rate increases dramatically during its course. This study was designed as an attempt to anatomically localize the inversion of the GABA response to norepinephrine. Because this phenomenon is observed in cortical slices and synaptosomes, it can be postulated that it occurs in the neocortex at the level of the intracortical GABA nerve terminals. Pharmacological analysis demonstrates that although the stimulation observed in controls is alpha-1 adrenoreceptor-mediated, the inhibition in tolerant animals is exerted via alpha-2 adrenoreceptors. Therefore, an increase in number or an improved coupling to the transduction system of alpha-2 adrenoreceptors is hypothesized. This observation gives a clue to a molecular interpretation of the inversion of GABA response to norepinephrine in tolerant animals, which may be of heuristic value in terms of biological interpretation of morphine tolerance.

Animals↗
PubMed1990

Regulation of endocrine function by the nicotinic cholinergic receptor.

One important neuroendocrine action of nicotine in the male rat is an increase in the secretion of corticosterone which is seen upon acute and acute intermittent exposure to nicotine. Tolerance develops to this action of nicotine upon chronic exposure, and in the withdrawal phase serum corticosterone levels are substantially reduced. In contrast, no significant increases of serum corticosterone levels were observed upon acute intermittent treatment with nicotine in the dioestrous rat. Available evidence indicates that corticosterone can modulate dopamine transmission in the basal ganglia via glucocorticoid receptors within the nucleus accumbens and neostriatum, and via glucocorticoid receptor immunoreactivity in nigrostriatal and mesolimbic dopamine pathways. Through concerted pre- and postsynaptic actions glucocorticoids may decrease dopamine transmission, especially that mediated by D2 receptors in these regions. In view of the hypothesis that the mesolimbic dopamine pathways mediate the euphoric effects of nicotine, the secretion of corticosterone induced by nicotine in the smoking male may substantially influence the mood elevating activity of nicotine. Thus, individual smoking habits may depend on the ability of nicotine to induce corticosterone secretion, which obviously would also vary with the degree of stress. The glucocorticoids may in a similar way influence the arousal action of nicotine because of the high number of glucocorticoid receptors present both in noradrenaline cell bodies of the locus ceruleus and within the entire cerebral cortex.

Animals↗
PubMed1990

Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors.

The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 microM but not 1 microM or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 microM and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s.c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 microM). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Changes in pituitary-adrenal activity affect the apomorphine- and cholecystokinin-8-induced changes in striatal dopamine release using microdialysis.

The effects of apomorphine (0.05 mg/kg, i.p.) and cholecystokinin-8 (sulphated; CCK-8) were analyzed on the levels of dopamine and its metabolites using intrastriatal microdialysis in the adrenalectomized rat with or without corticosterone replacement treatment (5 mg/kg, twice daily for 7 days, last dose given 2 h before killing). Adrenalectomy did not affect the basal release of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) or homovanillic acid (HVA). However, the apomorphine-induced decrease in dopamine release was attenuated following adrenalectomy. Furthermore, there was an enhancement of the apomorphine-induced decrease in DOPAC levels without any modulation of the apomorphine-induced effects on HVA levels. In contrast, the CCK-8-induced increase in dopamine levels was potentiated following adrenalectomy. This potentiation was fully counteracted by replacement treatment with corticosterone. These results indicate that corticosterone may be involved in the regulation of dopamine release, perhaps through glucocorticoid receptors in nigral dopamine cells controlling inter alia the synthesis of G-proteins involved in the regulation of dopamine autoreceptors and CCK-8 receptors located on dopamine nerve terminals or of the receptor proteins themselves.

3,4-Dihydroxyphenylacetic Acid↗