RESUMO
Cuticle tanning occurs in insects immediately after hatching or molting. During this process, the cuticle becomes dark and rigid due to melanin deposition and protein crosslinking. In insects, different from mammals, melanin is synthesized mainly from dopamine, which is produced from DOPA by the enzyme DOPA decarboxylase. In this work, we report that the silencing of the RpAadc-2 gene, which encodes the putative Rhodnius prolixus DOPA decarboxylase enzyme, resulted in a reduction in nymph survival, with a high percentage of treated insects dying during the ecdysis process or in the expected ecdysis period. Those treated insects that could complete ecdysis presented a decrease in cuticle pigmentation and hardness after molting. In adult females, the knockdown of AADC-2 resulted in a reduction in the hatching of eggs; the nymphs that managed to hatch failed to tan the cuticle and were unable to feed. Despite the failure in cuticle tanning, knockdown of the AADC-2 did not increase the susceptibility to topically applied deltamethrin, a pyrethroid insecticide. Additionally, our results showed that the melanin synthesis pathway did not play a major role in the detoxification of the excess (potentially toxic) tyrosine from the diet, an essential trait for hematophagous arthropod survival after a blood meal.
Assuntos
Dopa Descarboxilase/fisiologia , Proteínas de Insetos/fisiologia , Tegumento Comum/fisiologia , Rhodnius/enzimologia , Rhodnius/crescimento & desenvolvimento , Animais , Dopa Descarboxilase/farmacologia , Feminino , Inativação Metabólica , Proteínas de Insetos/farmacologia , Inseticidas , Melaninas/metabolismo , Muda/fisiologia , Nitrilas , Pigmentação/fisiologia , Piretrinas , Reprodução , Rhodnius/genética , Tirosina/metabolismoRESUMO
The enzyme DOPA decarboxylase (aromatic-L-amino-acid decarboxylase, DDC) plays an important role in the dopaminergic system and participates in the uptake and decarboxylation of amine precursors in the peripheral tissues. Apart from catecholamines, DDC catalyses the biosynthesis of serotonin and trace amines. It has been shown that the DDC amino acid sequence is highly evolutionarily conserved across many species. The activity of holoenzyme is regulated by stimulation/blockade of membrane receptors, phosphorylation of serine residues, and DDC interaction with regulatory proteins. A single gene codes for DDC both in neuronal and non-neuronal tissue, but synthesized isoforms of mRNA differ in the 5' UTR and in the presence of alternative exons. Tissue-specific expression of the DDC gene is controlled by two spatially distinct promoters - neuronal and non-neuronal. Several consensus sequences recognized by the HNF and POU family proteins have been mapped in the neuronal DDC promoter. Since DDC is located close to the imprinted gene cluster, its expression can be subjected to tightly controlled epigenetic regulation. Perturbations in DDC expression result in a range of neurodegenerative and psychiatric disorders and correlate with neoplasia. Apart from the above issues, the role of DDC in prostate cancer, bipolar affective disorder, Parkinson's disease and DDC deficiency is discussed in our review. Moreover, novel and prospective clinical treatments based on gene therapy and stem cells for the diseases mentioned above are described.
Assuntos
Dopa Descarboxilase/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Descarboxilases de Aminoácido-L-Aromático/deficiência , Descarboxilases de Aminoácido-L-Aromático/metabolismo , Catecolaminas/biossíntese , Dopa Descarboxilase/química , Dopa Descarboxilase/genética , Dopa Descarboxilase/fisiologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Doença de Parkinson/metabolismo , Neoplasias da Próstata/metabolismo , Conformação Proteica , Isoformas de Proteínas/metabolismo , Serotonina/biossínteseRESUMO
A central role for phenotypic plasticity in adaptive evolution is often posited yet lacks empirical support. Selection for the stable production of an induced phenotype is hypothesized to modify the regulation of preexisting developmental pathways, producing rapid adaptive change. We examined the role of plasticity in rapid adaptation of the zooplankton Daphnia melanica to novel fish predators. Here we show that plastic up-regulation of the arthropod melanin gene dopa decarboxylase (Ddc) in the absence of UV radiation is associated with reduced pigmentation in D. melanica. Daphnia populations coexisting with recently introduced fish exhibit environmentally invariant up-regulation of Ddc, accompanied by constitutive up-regulation of the interacting arthropod melanin gene ebony. Both changes in regulation are associated with adaptive reduction in the plasticity and mean expression of melanin. Our results provide evidence that the developmental mechanism underlying ancestral plasticity in response to an environmental factor has been repeatedly co-opted to facilitate rapid adaptation to an introduced predator.
Assuntos
Adaptação Fisiológica , Daphnia/fisiologia , Comportamento Predatório , Animais , Dopa Descarboxilase/fisiologia , Fenótipo , Raios Ultravioleta , Regulação para CimaRESUMO
Phagocytosis, melanization and nodulation in insects depend on phenoloxidase (PO) activity. In this report, we demonstrated that these three processes appear to be also dependent on dopa decarboxylase (Ddc) activity. Using flow cytometry, RNA interference, immunoprecipitation and immunofluorescence, we demonstrated the constitutive expression of Ddc and its strong association with the haemocyte surface, in the medfly Ceratitis capitata. In addition, we showed that Escherichia coli phagocytosis is markedly blocked by small interfering RNA (siRNA) for Ddc, antibodies against Ddc, as well as by inhibitors of Ddc activity, namely carbidopa and benzerazide, convincingly revealing the involvement of Ddc activity in phagocytosis. By contrast, latex beads and lipopolysaccharide (LPS) did not require Ddc activity for their uptake. It was also shown that nodulation and melanization processes depend on Ddc activation, because antibodies against Ddc and inhibitors of Ddc activity prevent haemocyte aggregation and melanization in the presence of excess E. coli. Therefore, phagocytosis, melanization and nodulation depend on haemocyte-surface-associated PO and Ddc. These three unrelated mechanisms are based on tyrosine metabolism and share a number of substrates and enzymes; however, they appear to be distinct. Phagocytosis and nodulation depend on dopamine-derived metabolite(s), not including the eumelanin pathway, whereas melanization depends exclusively on the eumelanin pathway. It must also be underlined that melanization is not a prerequisite for phagocytosis or nodulation. To our knowledge, the involvement of Ddc, as well as dopa and its metabolites, are novel aspects in the phagocytosis of medfly haemocytes.
Assuntos
Ceratitis capitata/imunologia , Dopa Descarboxilase/fisiologia , Hemócitos/metabolismo , Melaninas/biossíntese , Fagocitose/fisiologia , Animais , Ceratitis capitata/enzimologia , Ceratitis capitata/metabolismo , Di-Hidroxifenilalanina/metabolismo , Dopa Descarboxilase/genética , Escherichia coli/imunologia , Hemócitos/enzimologia , Imunidade Inata , RNA Interferente Pequeno/genéticaRESUMO
BACKGROUND: The androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis. RESULTS: Comparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR. CONCLUSION: Taken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.
Assuntos
Adenocarcinoma/enzimologia , Androgênios , Dopa Descarboxilase/fisiologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/fisiologia , Neoplasias Hormônio-Dependentes/enzimologia , Neoplasias da Próstata/enzimologia , Receptores Androgênicos/fisiologia , Adenocarcinoma/metabolismo , Western Blotting , Linhagem Celular Tumoral/metabolismo , Dopa Descarboxilase/genética , Indução Enzimática/efeitos dos fármacos , Perfilação da Expressão Gênica , Vetores Genéticos/farmacologia , Humanos , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Hormônio-Dependentes/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias da Próstata/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraciclina/farmacologia , TransfecçãoRESUMO
Molecular mechanisms that produce pigment patterns in the insect cuticle were studied. Larvae of the armyworm Pseudaletia separata have stripe patterns that run longitudinally along the body axis. The pattern in the cuticle became clear by being emphasized by the increasing contrast between the black and white colors of the lines after the last larval molt. We demonstrated that dopa decarboxylase (DDC) mRNA as well as protein are expressed specifically in the epidermal cells under the black stripes. The pigmentation on the stripes was clearly diminished by injection of a DDC inhibitor (m-hydroxybenzylhydrazine) to penultimate instar larvae for 1 day before molting, suggesting that DDC contributes to the production of melanin. Further, electron microscopic observation showed that the epidermal cells under the gap cuticle region (white stripe) between the black stripes contain many uric acid granules, which gives a white color. Our findings suggest that the spatially regulated expression of DDC in the epidermal cells produces the black stripes while abundant granules of uric acid in the cells generate the white stripes in the cuticle. Based on these results, we concluded that this heterogeneity in the epidermal cells forms cuticular stripe patterns in the armyworm larvae.
Assuntos
Dopa Descarboxilase/fisiologia , Larva/metabolismo , Mariposas/metabolismo , Pigmentação/fisiologia , Animais , Dopa Descarboxilase/metabolismo , Epiderme/metabolismo , Epiderme/ultraestrutura , Regulação da Expressão Gênica no Desenvolvimento , Larva/ultraestrutura , Melaninas/metabolismo , Mariposas/ultraestrutura , Fatores de Tempo , Ácido Úrico/metabolismoAssuntos
Dopamina/fisiologia , Transtornos Parkinsonianos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada de Emissão de Fóton Único , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Demência/diagnóstico por imagem , Diagnóstico Diferencial , Progressão da Doença , Dopa Descarboxilase/análise , Dopa Descarboxilase/fisiologia , Dopamina/análise , Proteínas da Membrana Plasmática de Transporte de Dopamina , Diagnóstico Precoce , Tremor Essencial/diagnóstico por imagem , Humanos , Radioisótopos do Iodo , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras/análise , Proteínas de Membrana Transportadoras/fisiologia , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/fisiologia , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/diagnóstico por imagem , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Compostos Radiofarmacêuticos/farmacocinética , Receptores Dopaminérgicos/análise , Receptores Dopaminérgicos/fisiologia , Proteínas Vesiculares de Transporte de Aminas BiogênicasRESUMO
Our hypothesis was tested in respect to dopamine synthesis by non-dopaminergic neurons expressing individual complementary enzymes of the DA synthetic pathway. According to the hypothesis, L-dihydroxyphenylalanine (L-DOPA) synthesised in tyrosine hydroxylase(TH)-expressing neurons for conversion to dopamine. The mediobasal hypothalamus of rats on the 21st embryonic day was used as an experimental model. The fetal substantia nigra containing dopaminergic neurons served as control. Dopamine and L-DOPA were measured by high performance liquid chromatography in cell extracts and incubation medium in presence or absence of L-tyrosine. L-tyrosine administration increased L-DOPA synthesis in the mediobasal hypothalamus and substantia nigra. Moreover, L-tyrosine provoked an increase of dopamine synthesis in substantia nigra and a decrease in the mediobasal hypothalamus. This is, probably, due to an L-tyrosine-induced competitive inhibition of the L-DOPA transport to monoenzymatic AADC neurons after its release from the monoenzymatic TH neurons. This study provides a convincing evidence of dopamine synthesis by non-dopaminergic neurons expressing TH or AADC, in cooperation.
Assuntos
Núcleo Arqueado do Hipotálamo/enzimologia , Dopamina/biossíntese , Neurônios/enzimologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Núcleo Arqueado do Hipotálamo/citologia , Extratos Celulares/química , Dopa Descarboxilase/fisiologia , Feto/citologia , Levodopa/análise , Levodopa/biossíntese , Ratos , Substância Negra/citologia , Tirosina/metabolismoRESUMO
The human striatum, especially its ventral part, the nucleus accumbens (Acc), contains numerous nonmonoaminergic aromatic L-amino acid decarboxylase (AADC) [=dopa decarboxylase (DDC)] neurons (D-neurons). AADC is the second-step synthesizing enzyme for monoamines and is also the rate-limiting enzyme of phenylethylamine (PEA) synthesis. D-neurons may participate in the manifestation of efficacy of pharmacotherapy for Parkinson's disease by taking up monoamine precursors including L-dopa or droxidopa (L-threo-DOPS) and by converting them to dopamine or noradrenaline, respectively. Although previous studies have shown that AADC activity was elevated in the striatum of drug-naive schizophrenia, the number of striatal D-neurons was reduced in autopsy brains of schizophrenia. It is unclear whether or not such reduction of striatal D-neurons implies downregulation. Possible pluripotentiality of D-neurons, including compensatory functions against aging and degeneration, was discussed based on recent published works.
Assuntos
Dopa Descarboxilase/fisiologia , Transtornos Mentais/fisiopatologia , Neostriado/fisiologia , Doenças do Sistema Nervoso/fisiopatologia , Neurônios/fisiologia , Animais , Antiparkinsonianos/uso terapêutico , Humanos , Levodopa/uso terapêutico , Sistema Límbico/fisiologia , Neostriado/citologia , Neostriado/fisiopatologia , Doenças do Sistema Nervoso/tratamento farmacológico , Neurônios/enzimologiaRESUMO
L-3,4-Dihydroxyphenylalanine (L-dopa) is the mainstay of therapy for patients with Parkinson's disease (PD), and mediates its primary effects through conversion into dopamine by aromatic L-amino acid decarboxylase (AADC). Given the loss of AADC-containing nigrostriatal dopaminergic neurons in PD, however, the location of residual AADC that converts L-dopa into dopamine remains controversial. The first objective of this study was to establish the presence of AADC expression in striatal neurons and glia using reverse transcriptase and PCR. Transcripts for the neuronal but not nonneuronal forms of AADC were detected in striatal tissue, cultured striatal neurons, and glia. We then examined whether this striatal AADC expression represents a physiologically significant source of dopaine production. No dopamine release was detected following incubation of striatal cultures with L-dopa or transduction with adenovirus expressing tyrosine hydoxylase. Our data establish the presence of AADC expression in the striatum both in vivo and in vitro, but suggest that striatal components do not represent a primary source of L-dopa decarboxylation following nigrostriatal denervation in rats. Understanding the source and localization of AADC is important in understanding the complications of L-dopa therapy and in designing rational therapeutic strategies for PD, including cellular transplantation and gene therapy.
Assuntos
Corpo Estriado/enzimologia , Dopa Descarboxilase/fisiologia , Dopamina/biossíntese , Levodopa/metabolismo , Doença de Parkinson/enzimologia , Adenoviridae/genética , Animais , Animais Recém-Nascidos , Técnicas de Cultura de Células , Corpo Estriado/citologia , Descarboxilação , Dopa Descarboxilase/genética , Feminino , Terapia Genética , Neuroglia/enzimologia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Transdução Genética , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
BACKGROUND: Animal melanin patterns are involved in diverse aspects of their ecology, from thermoregulation to mimicry. Many theoretical models have simulated pigment patterning, but little is known about the developmental mechanisms of color pattern formation. In Drosophila melanogaster, several genes are known to be necessary for cuticular melanization, but the involvement of these genes in melanin pattern evolution is unknown. We have taken a genetic approach to elucidate the developmental mechanisms underlying melanin pattern formation in various drosophilids. RESULTS: We show that, in D. melanogaster, tyrosine hydroxylase (TH) and dopa decarboxylase (DDC) are required for melanin synthesis. Ectopic expression of TH, but not DDC, alone was sufficient to cause ectopic melanin patterns in the wing. Thus, changes in the level of expression of a single gene can result in a new level of melanization. The ontogeny of this ectopic melanization resembled that found in Drosophila species bearing wing melanin patterns and in D. melanogaster ebony mutants. Importantly, we discovered that in D. melanogaster and three other Drosophila species these wing melanin patterns are dependent upon and shaped by the circulation patterns of hemolymph in the wing veins. CONCLUSIONS: Complex wing melanin patterns are determined by two distinct developmental mechanisms. Spatial prepatterns of enzymatic activity are established late in wing development. Then, in newly eclosed adults, melanin precursors gradually diffuse out from wing veins and are oxidized into dark brown or black melanin. Both the prepatterning and hemolymph-supplied components of this system can change during evolution to produce color pattern diversity.
Assuntos
Proteínas de Drosophila , Drosophila/metabolismo , Melaninas/biossíntese , Asas de Animais/irrigação sanguínea , Asas de Animais/metabolismo , Animais , Evolução Biológica , Padronização Corporal/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Dopa Descarboxilase/biossíntese , Dopa Descarboxilase/genética , Dopa Descarboxilase/fisiologia , Dopamina/farmacologia , Drosophila/anatomia & histologia , Drosophila/enzimologia , Feminino , Expressão Gênica , Proteínas de Insetos/genética , Masculino , Mutação , Fenótipo , Especificidade da Espécie , Tirosina 3-Mono-Oxigenase/biossíntese , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/fisiologia , Veias/anatomia & histologia , Veias/metabolismo , Asas de Animais/enzimologiaRESUMO
The paroxysmal dyskinesias constitute a heterogeneous group of disorders whose pathophysiologies and nosologies are still generally unknown. In a boy with severe, paroxysmal non-kinesigenic dyskinesia (PNKD), an invasive video-electrographic study demonstrated that his PNKD did not originate from the cortex, while a discharge was registered from the caudate nuclei. An 18FDG PET scan failed to show metabolic anomalies. A 18FDOPA and a 11C raclopride PET scans revealed a marked reduction in the density of presynaptic dopa decarboxylase activity in the striatum, together with an increased density of postsynaptic dopamine D2 receptors. These findings may suggest a chronic upregulation of postsynaptic dopa receptors, either because of an increase in their numbers or changes in their affinity. It remains unknown if these are secondary to reduced dopamine synthesis or altered release, or if the changes in striatal dopamine receptor binding are a primary or a compensatory mechanism.
Assuntos
Coreia/fisiopatologia , Corpo Estriado/fisiopatologia , Dopa Descarboxilase/fisiologia , Receptores de Dopamina D2/fisiologia , Adolescente , Mapeamento Encefálico , Núcleo Caudado/fisiologia , Coreia/diagnóstico , Eletroencefalografia , Humanos , Masculino , Receptores Pré-Sinápticos/fisiologia , Tomografia Computadorizada de Emissão , Gravação em VídeoRESUMO
Recent experimental reports concerning L-dihydroxyphenylalanine (L-DOPA) and aromatic L-amino acid decarboxylase (AADC, L-DOPA decarboxylase) are reviewed in this article. Both in vitro and in vivo data now suggest that L-DOPA is an endogenous neuroactive compound that is released from neurons and acts as a neurotransmitter or neuromodulator in the brain. Administration of exogenous L-DOPA affects dopamine receptor status, AADC activity, and mitochondrial oxidation in experimental animals. The type and severity of these effects depend on the duration of the treatment. These findings may partly explain the limited efficacy of L-DOPA therapy in Parkinson's disease (PD). AADC also plays a controlling role in the central nervous system, being a regulatory enzyme in the synthesis of a putative neuromodulator 2-phenylethylamine and other trace amines. Recent experimental findings on AADC activity and localisation are of importance because they suggest that striatal [18F]DOPA uptake used as an indicator of PD progression in positron emission tomography (PET) studies is likely to overestimate nigrostriatal integrity in advanced PD. Possible new PET tracers of presynaptic dopaminergic function are discussed in this context.
Assuntos
Encéfalo/fisiopatologia , Di-Hidroxifenilalanina/fisiologia , Dopa Descarboxilase/fisiologia , Neurotransmissores/fisiologia , Doença de Parkinson/fisiopatologia , Transmissão Sináptica/fisiologia , Animais , Mapeamento Encefálico , Corpo Estriado/fisiologia , Dopamina/fisiologia , Humanos , Tomografia Computadorizada de EmissãoRESUMO
In order to supplement the deficient catecholamine neurotransmitters, dopamine and noradrenaline, in parkinsonian brains, the following strategies have been tried: (1) the precursor amino acids, L-DOPA and L-threo-dihydroxyphenylserine (DOPS), (2) 6R-L-erythro-tetrahydrobiopterin (BPH4) as tyrosine hydroxylase (TH) cofactor and nicotinamide adenine dinucleotide (NADH) as cofactor of dihydropteridine reductase to stimulate TH, (3) brain transplant of TH-containing cells, (4) inhibitors of monoamine oxidase (MAO) and/or catechol O-methyltransferase (COMT) with or without L-DOPA or L-DOPS, and (5) dopamine receptor agonists. Among these strategies, the precursor, L-DOPA, L-DOPS, MAO and COMT inhibitors, and dopamine receptor agonists have proved to be clinically effective. As a new strategy, increase in deficient TH activity has been tried experimentally and clinically either by stimulation of residual TH activity by the cofactors, BPH4 or NADH, or by brain transplant of natural TH-containing cells (fetal substantia nigra) or genetically engineered TH-containing cells.
Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores de Catecol O-Metiltransferase , Corpo Estriado/enzimologia , Dopa Descarboxilase/fisiologia , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/enzimologia , Tirosina 3-Mono-Oxigenase/fisiologia , Corpo Estriado/efeitos dos fármacos , Dopamina/fisiologia , Humanos , Norepinefrina/fisiologia , Doença de Parkinson/tratamento farmacológico , Substância Negra/efeitos dos fármacos , Substância Negra/enzimologiaRESUMO
The effects of heterosexual interactions on the in vivo rate of regional brain monoamine synthesis were examined in the male rat. To this end, the animals were administered an inhibitor of cerebral aromatic L-amino acid decarboxylase, NSD-1015 (100 mg.kg-1 i.p.), and regional brain DOPA and 5-HTP accumulation, over a 15-35 min period of sexual interaction, was compared with the DOPA or 5-HTP accumulation in time-matched home cage controls. Using the DOPA and 5-HTP accumulation as an estimate for the rate of tyrosine and tryptophan hydroxylase activity, respectively, the present results demonstrate: (1) an increased demand on catecholamine synthesis in the neocortex, the amygdala and in the septal area; and (2) an increased dopamine and serotonin synthesis in the ventral striatum (excluding the olfactory tubercle), and in the dorsal striatum.
Assuntos
5-Hidroxitriptofano/metabolismo , Encéfalo/fisiologia , Di-Hidroxifenilalanina/metabolismo , Comportamento Sexual Animal/fisiologia , Animais , Inibidores das Descarboxilases de Aminoácidos Aromáticos , Encéfalo/efeitos dos fármacos , Mapeamento Encefálico , Copulação/fisiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Dopa Descarboxilase/fisiologia , Feminino , Hidrazinas/farmacologia , Masculino , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Ratos , Ratos Endogâmicos , Serotonina/fisiologia , Comportamento Sexual Animal/efeitos dos fármacosRESUMO
Dopaminergic neurons of retina are activated when rats are placed in a lighted environment. L-DOPA, the precursor of dopamine, was administered to rats that were housed either in the light or the dark. In the light more dopamine and its metabolite 3,4-dihydroxyphenylacetic acid were formed from L-DOPA when compared with animals given the same dose of L-DOPA, but kept in the dark. Our results suggest that the in vivo decarboxylation of DOPA may be modulated by neuronal activity in the rat retina.
Assuntos
Dopamina/biossíntese , Levodopa/metabolismo , Luz , Retina/metabolismo , Animais , Dopa Descarboxilase/fisiologia , Levodopa/administração & dosagem , Masculino , Ratos , Ratos Endogâmicos , Retina/efeitos dos fármacosRESUMO
When Manduca sexta larvae are allatectomized 5 h before head capsule slippage (HCS) in the final larval molt, the new larval cuticle contains granules that melanize 3 h before ecdysis when the ecdysteroid titer falls (Curtis et al. 1984). In both the epidermis and hemolymph of these allatectomized larvae dopamine was higher than dopa prior to and at the time of melanization. Dopamine also increased in the new cuticle as melanization began. Dopa decarboxylase (DDC) activity increased in the epidermis, cuticle, and fat body beginning 16 h after HCS, with a two-fold greater increase in the epidermis of allatectomized larvae. Both alpha-MDH and alpha-fluoromethyl-dopa inhibited epidermal DDC activity and inhibited melanization in vitro when dopa was used as a precursor. Addition of dopamine to the medium allowed melanization in the presence of the inhibitors. All these results indicate that dopamine is likely the primary precursor of cuticular melanin. The diphenoloxidase in the premelanin granules was activated in vivo between 19 and 21 h after HCS and was found to prefer dopamine to dopa and not to convert tyrosine to melanin. The activation of the prophenoloxidase was inhibited by 20-hydroxyecdysone (20-HE), both in vivo and in vitro, if hormone was given by 16 h after HCS. Infusion of 1.2 microgram/ml 20-HE into allatectomized larvae for 24 h from HCS prevented both the increase in DDC activity and the activation of the premelanin granules. Although the larvae ecdysed after a 15 h delay, melanization never occurred.
Assuntos
Descarboxilases de Aminoácido-L-Aromático/fisiologia , Catecol Oxidase/fisiologia , Dopa Descarboxilase/fisiologia , Ecdisterona/farmacologia , Melaninas/biossíntese , Animais , Di-Hidroxifenilalanina/metabolismo , Dopamina/metabolismo , Ativação Enzimática/efeitos dos fármacos , Larva/efeitos dos fármacos , Lepidópteros , Metamorfose Biológica/efeitos dos fármacosRESUMO
Fruit flies synthesize several monoamine neurotransmitters. Dopa decarboxylase (Ddc) mutations affect synthesis of two of these, dopamine and serotonin. Both transmitters are implicated in vertebrate and invertebrate learning. Therefore, we bred flies of various Ddc genotypes and tested their learning ability in positively and negatively reinforced learning tasks. Mutations in the Ddc gene diminished learning acquisition approximately in proportion to their effect on enzymatic activity. Courtship and mating sequences of the mutants appeared normal, except for one aspect of male courtship that had previously been shown to be experience dependent. In contrast, the effect on behavior patterns that do not involve learning--phototaxis, geotaxis, olfactory acuity, responsiveness to sucrose--was relatively slight under these conditions. Moderate Ddc mutations affected the acquisition of learned responses while leaving memory retention unaltered. This is in contrast to the mutations dunce , rutabaga , and amnesiac , which primarily affect short-term memory.
Assuntos
Descarboxilases de Aminoácido-L-Aromático/fisiologia , Comportamento Animal/fisiologia , Dopa Descarboxilase/fisiologia , Drosophila melanogaster/genética , Aprendizagem/fisiologia , Animais , Dopa Descarboxilase/genética , Dopamina/fisiologia , Memória/fisiologia , Mutação , Serotonina/fisiologia , Comportamento Sexual Animal/fisiologiaRESUMO
The autonomic nervous system may play an important role in tissue autoregulation as the neurohumoral transmission process has been shown to constitute the final common pathway by which the effects of many physiological and pharmacological substances are mediated. The effects of the administration of a sympathomimetic amine cannot be accurately predicted in a subject. Choice of which sympathomimetic amine to use should be determined on the basis of data obtained in relevant clinical circumstances, but the dose should always be titrated against the effect in each individual. It is interesting that adrenaline, "the original autonomic drug" with its "venerable history", is still a first line drug in many of the situations for which it was being prescribed in 1907. It is the drug of first choice in anaphylactic reactions and for severe allergic bronchospasm, and is widely used as a vasoconstrictor in surgery and with local anaesthetic agents. Adrenaline in "physiological" doses is a satisfactory and cheap alternative to other available drugs for use in septic shock and in emergence from cardiopulmonary bypass.