RESUMO
Odor transduction in the cilia of olfactory sensory neurons involves several ATP-requiring enzymes. ATP is generated by glycolysis in the ciliary lumen, using glucose incorporated from surrounding mucus, and by oxidative phosphorylation in the dendrite. During prolonged stimulation, the cilia maintain ATP levels along their length, by unknown means. We used immunochemistry, RT-PCR, and immunoblotting to explore possible underlying mechanisms. We found the ATP-shuttles, adenylate and creatine kinases, capable of equilibrating ATP. We also investigated how glucose delivered by blood vessels in the olfactory mucosa reaches the mucus. We detected, in sustentacular and Bowman's gland cells, the crucial enzyme in glucose secretion glucose-6-phosphatase, implicating both cell types as putative glucose pathways. We propose a model accounting for both processes.
Assuntos
Trifosfato de Adenosina/metabolismo , Cílios/metabolismo , Glucose-6-Fosfatase/metabolismo , Glucose/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Adenilato Quinase/genética , Adenilato Quinase/metabolismo , Animais , Transporte Biológico , Membrana Celular/metabolismo , Membrana Celular/ultraestrutura , Cerebelo/citologia , Cerebelo/metabolismo , Cílios/ultraestrutura , Creatina Quinase Forma BB/genética , Creatina Quinase Forma BB/metabolismo , Expressão Gênica , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glucose-6-Fosfatase/genética , Glicólise , Masculino , Microssomos/metabolismo , Microssomos/ultraestrutura , Neurônios Receptores Olfatórios/citologia , Fosforilação Oxidativa , Ratos , Ratos Sprague-Dawley , Técnicas de Cultura de TecidosRESUMO
Organotellurium compounds have been synthesized since 1840, but their pharmacological and toxicological properties are still incipient. Therefore, the objective of this study was to verify the effect of acute administration with the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on the activity of brain creatine kinase (CK), a key enzyme in energy metabolism, and on behaviors in the open field test of 30-day-old rats. Animals were treated intraperitoneally with a single dose of the organotellurium (125, 250, or 500 µg/kg body weight) and after 55 min of the drug administration the open field test was carried out. Behavior analyses were performed during 5 min and the number of the squares crossed, number of rearing, number of groomings and number of fecal boli were recorded by an observer. Then, the animals were sacrificed and the cerebral cortex, the hippocampus, and the cerebellum were dissected, and CK activity and sulfhydryl content were measured in the brain. The organotellurium increased the ambulation and rearing behaviors in the open field test at doses of 250 and 500 µg/kg. Moreover, the compound inhibited CK activity and provoked a reduced of thiol content measured by the sulfhydryl assay in all the tissues studied. Therefore, changes in energy homeostasis and motor behavior in rats treated with this organotellurium support the hypotheses that the brain is a potential target to pharmacological and toxicological effects of this compound.
Assuntos
Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Compostos Organometálicos/farmacologia , Animais , Creatina Quinase Forma BB/antagonistas & inibidores , Creatina Quinase Forma BB/metabolismo , Metabolismo Energético , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismoRESUMO
Bipolar disorder (BD) is a common and severe mood disorder associated with higher rates of suicide and disability. The development of new animal models, and the investigation employing those available have extensively contributed to understand the pathophysiological mechanisms of BD. Intracerebroventricular (i.c.v.) administration of ouabain, a specific Na+,K+-ATPase inhibitor, has been used as an animal model for BD. It has been demonstrated that Na+,K+-ATPase is altered in psychiatric disorders, especially BD. Creatine kinase (CK) is important for brain energy homeostasis by exerting several integrated functions. In the present study,we evaluated CK activity in the striatum, prefrontal cortex and hippocampus of rats subjected to i.c.v. administration of ouabain. Adult male Wistar rats received a single i.c.v. administration of ouabain (10(-2) and 10(-3) M) or vehicle (control group). Locomotor activity was measured using the open field test. CK activity was measured in the brain of rats immediately (1 h) and 7 days after ouabain administration. Our results showed that spontaneous locomotion was increased 1 h after ouabain administration and that hyperlocomotion was also observed 7 days after that.Moreover, CK activity was inhibited immediately after the administration of ouabain in the striatum, hippocampus and prefrontal cortex. Moreover, the enzyme was not affected in the striatum and hippocampus 7 days after ouabain administration. On the other hand, an inhibition in CK activity in the prefrontal cortex was observed. If inhibition of CK also occurs in BD patients, it will be tempting to speculate that the reduction of brain metabolism may be related probably to the pathophysiology of this disease.
Assuntos
Transtorno Bipolar/enzimologia , Corpo Estriado/enzimologia , Creatina Quinase Forma BB/metabolismo , Hipocampo/enzimologia , Córtex Pré-Frontal/enzimologia , Animais , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/metabolismo , Corpo Estriado/metabolismo , Creatina Quinase Forma BB/antagonistas & inibidores , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Atividade Motora , Ouabaína , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
BACKGROUND: Mating changes the mode of action of 17beta-estradiol (E2) to accelerate oviductal egg transport from a nongenomic to a genomic mode, although in both pathways estrogen receptors (ER) are required. This change was designated as intracellular path shifting (IPS). METHODS: Herein, we examined the subcellular distribution of ESR1 and ESR2 (formerly known as ER-alpha and ER-beta) in oviductal epithelial cells of rats on day 1 of cycle (C1) or pregnancy (P1) using immunoelectron microscopy for ESR1 and ESR2. The effect of mating on intraoviductal ESR1 or ESR2 signaling was then explored comparing the expression of E2-target genes c-fos, brain creatine kinase (Ckb) and calbindin 9 kDa (s100g) in rats on C1 or P1 treated with selective agonists for ESR1 (PPT) or ESR2 (DPN). The effect of ER agonists on egg transport was also evaluated on C1 or P1 rats. RESULTS: Receptor immunoreactivity was associated with the nucleus, cytoplasm and plasma membrane of the epithelial cells. Mating affected the subcellular distribution of both receptors as well as the response to E2. In C1 and P1 rats, PPT increased Ckb while both agonists increased c-fos. DPN increased Ckb and s100g only in C1 and P1 rats, respectively. PPT accelerated egg transport in both groups and DPN accelerated egg transport only in C1 rats. CONCLUSION: Estrogen receptors present a subcellular distribution compatible with E2 genomic and nongenomic signaling in the oviductal epithelial cells of C1 and P1 although IPS occurs independently of changes in the distribution of ESR1 and ESR2 in the oviductal epithelial cells. Mating affected intraoviductal ER-signaling and induced loss of functional involvement of ESR2 on E2-induced accelerated egg transport. These findings reveal a profound influence on the ER signaling pathways exerted by mating in the oviduct.
Assuntos
Tubas Uterinas/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Calbindinas , Creatina Quinase Forma BB/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Ciclo Estral/genética , Ciclo Estral/metabolismo , Tubas Uterinas/efeitos dos fármacos , Tubas Uterinas/fisiologia , Feminino , Ginsenosídeos/farmacologia , Nitrilas/farmacologia , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/agonistas , Receptores de Estrogênio/genética , Proteína G de Ligação ao Cálcio S100/metabolismo , Sapogeninas/farmacologia , Distribuição TecidualRESUMO
Recently, a fixed combination of the atypical antipsychotic olanzapine and the serotonin selective reuptake inhibitor (SSRI) fluoxetine has been approved in the US for the treatment of bipolar I depression. In this work, we evaluated the effect of acute and chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on creatine kinase (CK) activity in the brain of rats. For acute treatment, adult male Wistar rats received one single injection of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg). For chronic treatment, adult male Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days. In the present study we observed that acute administration of OLZ inhibited CK activity in cerebellum and prefrontal cortex. The acute administration of FLX inhibited creatine kinase in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex. In the chronic treatment, when the animals were killed 2h after the last injection a decrease in creatine kinase activity after FLX administration, alone or in combination with OLZ, in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex of rats occurred. However, when the animals were killed 24h after the last injection, we found no alterations in the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of creatine kinase activity by these drugs may be associated to the occurrence of some side effects of OLZ and FLX.
Assuntos
Antipsicóticos/farmacologia , Benzodiazepinas/farmacologia , Encéfalo/efeitos dos fármacos , Creatina Quinase Forma BB/antagonistas & inibidores , Fluoxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Análise de Variância , Animais , Antipsicóticos/administração & dosagem , Benzodiazepinas/administração & dosagem , Encéfalo/enzimologia , Encéfalo/metabolismo , Creatina Quinase Forma BB/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Fluoxetina/administração & dosagem , Masculino , Olanzapina , Ratos , Ratos Wistar , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagemRESUMO
Major depression is a serious and recurrent disorder often manifested with symptoms at the psychological, behavioral, and physiological levels. In addition, several works also suggest brain metabolism impairment as a mechanism underlying depression. Creatine kinase (CK) plays a central role in the metabolism of high-energy consuming tissues such as brain, where it functions as an effective buffering system of cellular ATP levels. Considering that CK plays an important role in brain energy homeostasis and that some antidepressants may modulate energy metabolism, we decided to investigate CK activity from rat brain after chronic administration of paroxetine (selective serotonin reuptake inhibitor), nortriptiline (tricyclic antidepressant) and venlafaxine (selective serotonin-norepinephrine reuptake inhibitor). Adult male Wistar rats received daily injections of paroxetine (10 mg/kg), nortriptiline (15 mg/kg), venlafaxine (10 mg/kg) or saline in 1.0 mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activity of CK was measured. Our results demonstrated that chronic administration of paroxetine increased CK activity in the prefrontal cortex, hippocampus and striatum of adult rats. On the other hand, nortriptiline and venlafaxine chronic administration did not affect CK activity in these brain areas. In order to verify whether the effect of paroxetine on CK is direct or indirect, we also measured the in vitro effect of this drug on the activity of the enzyme. We verified that paroxetine did not affect CK activity in vitro. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in CK activity by antidepressants may be an important mechanism of action of these drugs.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Creatina Quinase Forma BB/metabolismo , Paroxetina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos Tricíclicos/farmacologia , Encéfalo/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/enzimologia , Corpo Estriado/metabolismo , Cicloexanóis/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/metabolismo , Masculino , Nortriptilina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/enzimologia , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Cloridrato de VenlafaxinaRESUMO
Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensory-motor deficits, seizures, and impairments of learning and memory. Creatine kinase (CK) is an effective buffering system of cellular ATP levels in high-energy consuming tissues; a decrease in CK activity is associated with a neurodegenerative pathway that results in neuronal loss. Thus, the aim of this study was to evaluate brain CK activity after pneumococcal meningitis. The animals underwent a magna cistern tap receiving either sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension; they were killed 6, 12, 24 and 48h after that, the brain was removed and hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used for the determination of CK activity. We verified that CK activity was not altered 6 and 12h after meningitis. Interestingly, 24h after the induction of the meningitis we observed a decrease in CK activity. Finally, CK activity was not altered 48h after meningitis. Although it is difficult to extrapolate our findings to the human condition, the inhibition of brain CK activity may be involved in the pathogenesis of pneumococcal meningitis.