RESUMO
OBJECTIVES: Progesterone modulates dopamine (DA) release in corpus striatum. Our objective was to evaluate the effect of the i.c.v injection of the neurosteroid allopregnanolone (ALL), a progesterone metabolite on dopaminergic activity in the corpus striatum of rats under different gonadal hormonal conditions. METHODS: We have measured the concentrations of DOPA, DA and DOPAC (main metabolite of DA) in the corpus striatum in estrus and diestrus rats and in ovariectomized rats without hormonal replacement (OVX group) and primed with estrogen and progesterone (OVX(i) group). Additionally, we have used the aromatic acid decarboxylase inhibitor NSD in order to evaluate the function of tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine synthesis. RESULTS: ALL significantly decreased the striatal concentrations of both DA and DOPAC in the estrus. On the other hand, ALL increased significantly the levels of DA in the OVX(i) group. The DOPA accumulation in OVX(i) after NSD treatment in the ALL-treated groups was greater than in the vehicle group. However, the estrus group did not modify the DOPA accumulation after NSD injection. DISCUSSION: Our results suggest that ALL could modulate the dopaminergic transmission in the corpus striatum by causing changes in the activity of TH and/or in the pre- and post-synaptic dopaminergic terminals in the corpus striatum. This neurosteroidal mechanism could be a new kind of neurotransmitter systems modulation accomplished on TH activity itself and/or on the second messengers not related to ionic channels. Additionally, our results reinforce the idea of a close relationship between the fast non-genomic mechanism of ALL and the genomic actions of estrogen and progesterone.
Assuntos
Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Hormônios Gonadais/fisiologia , Pregnanolona/farmacologia , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Análise de Variância , Anestésicos , Animais , Di-Hidroxifenilalanina/metabolismo , Ciclo Estral , Feminino , Atividade Motora/efeitos dos fármacos , Ovariectomia/métodos , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
TNFa has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFa on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFa. RT-PCR analysis showed that SW756 cells express TNFa mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFa (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFa antibody or both TNFa and anti-TNFa antibody (p<0.05). The results showed a stimulatory effect of TNFa on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFa in cervical cancer progression.
Assuntos
Feminino , Humanos , Carcinoma/microbiologia , Movimento Celular/efeitos dos fármacos , /genética , Fator de Necrose Tumoral alfa/farmacologia , Neoplasias do Colo do Útero/microbiologia , Linhagem Celular Tumoral , Meios de Cultura Livres de Soro , Carcinoma/genética , Carcinoma/patologia , Proliferação de Células/efeitos dos fármacos , /isolamento & purificação , Processamento de Imagem Assistida por Computador , Cinética , Microscopia de Vídeo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Mensageiro/metabolismo , Proteínas Recombinantes/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Cicatrização/efeitos dos fármacosRESUMO
The gonadotropes, LH and FSH cells, were immunohistochemically identified in the pituitary pars distalis of the adult male viscacha (Lagostomus maximus maximus) using specific antibodies against hLHbeta and hFSHbeta with the streptavidin-biotin-peroxidase complex. The distribution, size and percentage immunopositive area of these cells were analyzed by image analysis in viscachas captured during the annual reproductive cycle and after the chronic administration of melatonin. The LHbeta and FSHbeta cells showed seasonal changes in the distribution, size and percentage immunopositive area. The LHbeta cells were found widely distributed throughout the pars distalis during the reproductive period, and they were found in the ventro-medial region in the pars distalis during the gonadal regression and gonadal recovery periods. The LHbeta cells reached the largest size and immunopositive area during the reproductive period and the smallest size and immunopositive area during the gonadal regression period. The FSHbeta cells were found in the ventro-medial region during reproductive and gonadal regression periods. The FSHbeta cells were found widely distributed throughout the pars distalis during the gonadal recovery period when they showed the maximum percentage immunopositive area. A decrease in the size of LHbeta and FSHbeta cells was observed after the chronic administration of melatonin. Moreover, it produces a decrease in the immunopositive area occupied by the LHbeta cells but not in the immunopositive area occupied by the FSHbeta cells. Our results show great activity of LHbeta and FSHbeta cells in different moments of the annual reproductive cycle demonstrating that these cells do not secrete in parallel. Moreover, melatonin acts differentially on the activity of the gonadotrope cells.
Assuntos
Gonadotropinas Hipofisárias/metabolismo , Melatonina/farmacologia , Adeno-Hipófise/fisiologia , Roedores/fisiologia , Estações do Ano , Vesículas Secretórias/fisiologia , Animais , Peso Corporal , Gonadotropinas Hipofisárias/análise , Imuno-Histoquímica , Masculino , Adeno-Hipófise/efeitos dos fármacos , Adeno-Hipófise/ultraestrutura , Vesículas Secretórias/efeitos dos fármacos , Vesículas Secretórias/ultraestrutura , Fatores de TempoRESUMO
TNFalpha has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFalpha on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFalpha. RT-PCR analysis showed that SW756 cells express TNFalpha mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFalpha (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFalpha antibody or both TNFalpha and anti-TNFalpha antibody (p < 0.05). The results showed a stimulatory effect of TNFalpha on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFalpha in cervical cancer progression.
Assuntos
Carcinoma/microbiologia , Movimento Celular/efeitos dos fármacos , Papillomavirus Humano 18/genética , Fator de Necrose Tumoral alfa/farmacologia , Neoplasias do Colo do Útero/microbiologia , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Meios de Cultura Livres de Soro , Feminino , Papillomavirus Humano 18/isolamento & purificação , Humanos , Processamento de Imagem Assistida por Computador , Cinética , Microscopia de Vídeo , RNA Mensageiro/metabolismo , Proteínas Recombinantes/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias do Colo do Útero/genética , Cicatrização/efeitos dos fármacosRESUMO
TNFalpha has been associated with both, tumor survival and apoptosis. This cytokine is also involved in promoting cell migration during wound healing and tumorigenesis. SW756 is a HPV18-positive cervical carcinoma cell line, which has been used to study different mechanisms of cervical cancer progression. An in vitro assay of scratch wound healing onto monolayers of SW756 cells was used to assess the effect of TNFalpha on cell migration into a wound space. It was found that SW756 cells have the ability to migrate, but not proliferate in response to scratch wounding in a serum-free medium supplemented with TNFalpha. RT-PCR analysis showed that SW756 cells express TNFalpha mRNA when incubated in medium with and without serum. Wound closure and migration rate of SW756 cells were significantly increased in the presence of serum-free media supplemented with TNFalpha (10 ng/mL) as compared to serum-free media, and media supplemented with either anti-TNFalpha antibody or both TNFalpha and anti-TNFalpha antibody (p < 0.05). The results showed a stimulatory effect of TNFalpha on the migration of SW756 cervical carcinoma cells, suggesting a novel and important role for TNFalpha in cervical cancer progression.
RESUMO
Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review.
Assuntos
Humanos , Feminino , Gravidez , Mastócitos/metabolismo , Parto/fisiologia , Útero/metabolismo , Contração Muscular/fisiologia , Hormônio Liberador da Corticotropina/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Mastócitos/citologia , Músculo Liso/fisiologia , Ocitocina/metabolismo , Útero/citologiaRESUMO
Birth is the result of complex, well-defined, and coordinated events, that are tightly regulated by endocrine, nervous, and immune responses, and take place primarily in the female reproductive tract. Various mechanisms and mediators involved in pregnancy, labor, and delivery, are highly conserved among different mammalian species and mast cells emerge as potential and crucial participants in these processes, as it is discussed in this review. (AU)
Assuntos
Humanos , Feminino , Gravidez , RESEARCH SUPPORT, NON-U.S. GOVT , Mastócitos/metabolismo , Parto/fisiologia , Útero/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Mastócitos/citologia , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Ocitocina/metabolismo , Útero/citologiaRESUMO
The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators.
Assuntos
Humanos , Sistema Digestório , Mastócitos/citologia , Mastócitos/imunologia , Anti-Inflamatórios , Imunidade nas Mucosas/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Lactonas/farmacologia , Lactonas/uso terapêutico , Mastócitos/efeitos dos fármacos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators. (AU)
Assuntos
Humanos , Sistema Digestório/citologia , Sistema Digestório/imunologia , Mastócitos/citologia , Mastócitos/imunologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Mucosa Gástrica/citologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Imunidade nas Mucosas/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Lactonas/farmacologia , Lactonas/uso terapêutico , Mastócitos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêuticoRESUMO
OBJECTIVE AND DESIGN: DhL, a lactone isolated from Artemisia douglasiana, prevents gastrointestinal damage elicited by necrosis-inducing agents and exhibits antiinflammatory action. This work examines the effect of DhL on compound 48/80-induced histamine and serotonin release in the isolated mouse jejunum, to determine whether DhL inhibits mediator release from mast cells at the enteric level. MATERIAL: Thirty jejuna from male Balb-c mice were used for the studies. TREATMENT: Samples were incubated sequentially in 9 test tubes containing RBS or 10 microg/ml compound 48/80 or 1.6 mmol/l + 10 microg/ml compound 48/80 at 37 degrees C for 90 minutes (10 min per tube). METHODS: Histamine and serotonin release studies, quantification of granulated mast cells, and evaluation of mast cell ultrastructure were carried out. Differences between groups were determined using analysis of variance followed by Tukey-Kramer multiple comparisons test. RESULTS: Compound 48/80 increased histamine and serotonin release by the tissue (141.95 +/- 62.58 pg/mg tissue vs basal 5.45 +/- 1.04, P<0.01 and 20.04 +/- 2.81 vs basal 9.24 +/- 1.56 ng/ mg tissue, P<0.01, respectively), decreased the number of granulated submucosal mast cells (0.077 +/- 0.0035 vs basal 0.14 +/- 0.015, P<0.05), and elicited evident granule ultrastructural changes. These effects were reduced by dehydroleucodine (19.51 +/- 7.88, P<0.01; 12.69 +/- 1, P<0.05 and 0.143 +/- 0.014, P<0.05, respectively). CONCLUSION: The lactone inhibits compound 48/80-induced histamine and serotonin release from mast cells in the isolated mouse jejunum.