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1.
Artigo em Inglês | MEDLINE | ID: mdl-31096708

RESUMO

Hormones are secreted in a circadian rhythm, but also follow larger-scale timetables, such as monthly (hormones of the menstrual cycle), seasonal (i.e., winter, summer), and, ultimately, lifespan-related patterns. Several contexts modulate their secretion, such as genetics, lifestyle, environment, diet, and exercise. They play significant roles in human physiology, influencing growth of muscle, bone, and regulating metabolism. Exercise training alters hormone secretion, depending on the frequency, duration, intensity, and mode of training which has an impact on the magnitude of the secretion. However, there remains ambiguity over the effects of exercise training on certain hormones such as glucoregulatory hormones in aging adults. With advancing age, there are many alterations with the endocrine system, which may ultimately alter human physiology. Some recent studies have reported an anti-aging effect of exercise training on the endocrine system and especially cortisol, growth hormone and insulin. As such, this review examines the effects of endurance, interval, resistance and combined training on hormones (i.e., at rest and after) exercise in older individuals. We summarize the influence of age on glucoregulatory hormones, the influence of exercise training, and where possible, examine masters' athletes' endocrinological profile.


Assuntos
Envelhecimento/fisiologia , Exercício Físico/fisiologia , Catecolaminas/fisiologia , Glucagon/fisiologia , Humanos , Hidrocortisona/fisiologia , Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia
2.
J Med Biogr ; 27(3): 179-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30848165

RESUMO

Hermann (Hugh) Blaschko was a biochemical pharmacologist best known for discovering how adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine were synthesized, stored, and metabolized in adrenomedullary cells and sympathetic nerves. Blaschko's work not only supported the validity of the concept of neurochemical synaptic transmission but he also made fundamental contributions to the development of drugs used in clinical medicine to treat diseases such as depression, hypertension, and Parkinson's Disease.


Assuntos
Bioquímica/história , Medicina Clínica/história , Farmacologia/história , Catecolaminas/história , Catecolaminas/fisiologia , Inglaterra , Alemanha , História do Século XX , Transmissão Sináptica/fisiologia
4.
Brain Res ; 1702: 54-73, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29705605

RESUMO

The success of anti-retroviral therapy has improved the quality of life and lifespan of HIV + individuals, transforming HIV infection into a chronic condition. These improvements have come with a cost, as chronic HIV infection and long-term therapy have resulted in the emergence of a number of new pathologies. This includes a variety of the neuropathological and neurocognitive effects collectively known as HIVassociated neurocognitive disorders (HAND) or NeuroHIV. These effects persist even in the absence of viral replication, suggesting that they are mediated the long-term changes in the CNS induced by HIV infection rather than by active replication. Among these effects are significant changes in catecholaminergic neurotransmission, especially in dopaminergic brain regions. In HIV-infected individuals not treated with ARV show prominent neuropathology is common in dopamine-rich brain regions and altered autonomic nervous system activity. Even infected individuals on therapy, there is significant dopaminergic neuropathology, and elevated stress and norepinephrine levels correlate with a decreased effectiveness of antiretroviral drugs. As catecholamines function as immunomodulatory factors, the resultant dysregulation of catecholaminergic tone could substantially alter the development of HIVassociated neuroinflammation and neuropathology. In this review, we discuss the role of catecholamines in the etiology of HIV neuropathogenesis. Providing a comprehensive examination of what is known about these molecules in the context of HIV-associated disease demonstrates the importance of further studies in this area, and may open the door to new therapeutic strategies that specifically ameliorate the effects of catecholaminergic dysregulation on NeuroHIV.


Assuntos
Catecolaminas/metabolismo , Infecções por HIV/metabolismo , Doenças do Sistema Nervoso/metabolismo , Catecolaminas/fisiologia , Dopamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Receptores Adrenérgicos beta/metabolismo
6.
Adv Exp Med Biol ; 1090: 199-210, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30390292

RESUMO

Lipolysis is a critical process to hydrolyze triglyceride in adipose tissue, thereby breaking down the stored lipid and maintaining energy homeostasis. Recent studies have made significant progress in understanding the steps of lipolysis. This chapter discusses the major pathways that regulate lipolysis in adipose tissue. Specifically we focus on the mechanisms by which the activities of critical lipolytic enzymes are regulated. We further discuss how the lipolysis is regulated by other factors, including insulin and neurotransmitters, in particular catecholamines and the role of sympathetic nervous system in the whole process. Finally we provide clinical perspectives about the novel therapeutic strategies to target or promote adipose tissue lipolysis for treatment/prevention of obesity and type 2 diabetes.


Assuntos
Tecido Adiposo/fisiologia , Lipólise , Catecolaminas/fisiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Metabolismo Energético , Homeostase , Humanos , Lipase/metabolismo , Obesidade/prevenção & controle , Sistema Nervoso Simpático/fisiologia , Triglicerídeos/metabolismo
7.
J Comp Neurol ; 526(14): 2319-2338, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30325514

RESUMO

The nucleus of the solitary tract is a potential site for taste-visceral interactions. Connections from the caudal, visceral area of the nucleus (cNST) to the rostral, gustatory zone (rNST) have been described, but the phenotype of cells giving rise to the projection(s) and their distribution among rNST subdivisions are unknown. To determine these characteristics of the intrasolitary pathway, we injected pan-neuronal and floxed AAV viruses into the cNST of mice expressing cre in glutamatergic, GABAergic, or catecholaminergic neurons. Particular attention was paid to the terminal field distribution in rNST subdivisions by simultaneously visualizing P2X2 localized to gustatory afferent terminals. All three phenotypically identified pathways terminated in rNST, with the density greatest for glutamatergic and sparsest for catecholaminergic projections, observations supported by retrograde tracing. Interestingly, cNST neurons had more prominent projections to rNST regions medial and ventral to P2X2 staining, i.e., the medial and ventral subdivisions. In addition, GABAergic neurons projected robustly to the lateral subdivision and adjacent parts of the reticular formation and spinal trigeminal nucleus. Although cNST neurons also projected to the P2X2-rich central subdivision, such projections were sparser. These findings suggest that cNST visceral signals exert stronger excitatory and inhibitory influences on local autonomic and reflex pathways associated with the medial and ventral subdivisions compared to weaker modulation of ascending pathways arising from the central subdivision and ultimately destined for the forebrain.


Assuntos
Neurônios/fisiologia , Núcleo Solitário/citologia , Animais , Catecolaminas/fisiologia , Feminino , Ácido Glutâmico/fisiologia , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia , Neurônios Aferentes/fisiologia , Prosencéfalo/citologia , Prosencéfalo/fisiologia , Receptores Purinérgicos P2X2/metabolismo , Paladar/fisiologia , Ácido gama-Aminobutírico/fisiologia
8.
Brain Res ; 1701: 177-188, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30217439

RESUMO

Vocal species use acoustic signals to facilitate diverse behaviors such as mate attraction and territorial defense. However, little is known regarding the neural substrates that interpret such divergent conspecific signals. Using the plainfin midshipman fish model, we tested whether specific catecholaminergic (i.e., dopaminergic and noradrenergic) nuclei and nodes of the social behavior network (SBN) are differentially responsive following exposure to playbacks of divergent social signals in sneaker males. We chose sneaker (type II) males since they attempt to steal fertilizations from territorial type I males who use an advertisement call (hum) to attract females yet are also subjected to vocal agonistic behavior (grunts) by type I males. We demonstrate that induction of cFos (an immediate early gene product and proxy for neural activation) in two forebrain dopaminergic nuclei is greater in sneaker males exposed to hums but not grunts compared to ambient noise, suggesting hums preferentially activate these nuclei, further asserting dopamine as an important regulator of social-acoustic behaviors. Moreover, acoustic exposure to social signals with divergent salience engendered contrasting shifts in functional connectivity between dopaminergic nuclei and nodes of the SBN, supporting the idea that interactions between these two circuits may underlie adaptive decision-making related to intraspecific male competition.


Assuntos
Batracoidiformes/fisiologia , Neurônios Dopaminérgicos/fisiologia , Comportamento Sexual Animal/fisiologia , Estimulação Acústica/métodos , Neurônios Adrenérgicos/fisiologia , Animais , Percepção Auditiva/fisiologia , Batracoidiformes/metabolismo , Catecolaminas/fisiologia , Núcleo Celular , Audição/fisiologia , Masculino , Reprodução/fisiologia , Comportamento Social , Vocalização Animal/fisiologia
9.
Arq Bras Cir Dig ; 31(3): e1383, 2018 Aug 16.
Artigo em Inglês, Português | MEDLINE | ID: mdl-30133675

RESUMO

BACKGROUND: The role of autonomic nervous system in the development and maintenance of portal hypertension is not fully elucidated. It is known that the gene expression of norepinephrine in the superior mesenteric artery varies with time, and it may contribute for splanchnic vasodilation and its consequent hemodynamic repercussions. It is still not known exactly how the adrenergic expression behaves at the heart level in the initial stages of this process. AIM: To evaluate the immunohistochemical expression of the enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), involved in the synthesis of norepinephrine, in the myocardium of rats submitted to partial ligation of the portal vein. METHODS: Twenty-four Wistar rats were divided into two groups: Sham Operated and Portal Hypertension. The partial ligation was performed in the Portal Hypertension group, and after 1/6/24 h and 3/5/14 days the animals were euthanized. Immunohistochemical analysis was performed to quantify the expression of the stained enzyme using the ImageJ program. RESULTS: The Portal Hypertension group expressed percentages between 4.6-6% of the marked area, while the Sham Operated group varied between 4-5%. Although there was no statistical significance, the percentage stained in the Portal Hypertension group followed an increasing pattern in the first 6 h and a decreasing pattern after 24 h, which was not observed in the Sham Operated group. CONCLUSION: The expression of noradrenaline in rat myocardium during the first two weeks after partial ligation of the portal vein, with tyrosine hydroxylase as marker, did not show differences between groups over time.


Assuntos
Hipertensão Portal/etiologia , Miocárdio/metabolismo , Norepinefrina/biossíntese , Animais , Catecolaminas/fisiologia , Modelos Animais de Doenças , Masculino , Norepinefrina/fisiologia , Ratos , Ratos Wistar , Tirosina 3-Mono-Oxigenase/biossíntese
10.
J Neurosci ; 38(34): 7476-7491, 2018 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-30037827

RESUMO

The widely projecting catecholaminergic (norepinephrine and dopamine) neurotransmitter systems profoundly shape the state of neuronal networks in the forebrain. Current models posit that the effects of catecholaminergic modulation on network dynamics are homogeneous across the brain. However, the brain is equipped with a variety of catecholamine receptors with distinct functional effects and heterogeneous density across brain regions. Consequently, catecholaminergic effects on brainwide network dynamics might be more spatially specific than assumed. We tested this idea through the analysis of fMRI measurements performed in humans (19 females, 5 males) at "rest" under pharmacological (atomoxetine-induced) elevation of catecholamine levels. We used a linear decomposition technique to identify spatial patterns of correlated fMRI signal fluctuations that were either increased or decreased by atomoxetine. This yielded two distinct spatial patterns, each expressing reliable and specific drug effects. The spatial structure of both fluctuation patterns resembled the spatial distribution of the expression of catecholamine receptor genes: α1 norepinephrine receptors (for the fluctuation pattern: placebo > atomoxetine), D2-like dopamine receptors (pattern: atomoxetine > placebo), and ß norepinephrine receptors (for both patterns, with correlations of opposite sign). We conclude that catecholaminergic effects on the forebrain are spatially more structured than traditionally assumed and at least in part explained by the heterogeneous distribution of various catecholamine receptors. Our findings link catecholaminergic effects on large-scale brain networks to low-level characteristics of the underlying neurotransmitter systems. They also provide key constraints for the development of realistic models of neuromodulatory effects on large-scale brain network dynamics.SIGNIFICANCE STATEMENT The catecholamines norepinephrine and dopamine are an important class of modulatory neurotransmitters. Because of the widespread and diffuse release of these neuromodulators, it has commonly been assumed that their effects on neural interactions are homogeneous across the brain. Here, we present results from the human brain that challenge this view. We pharmacologically increased catecholamine levels and imaged the effects on the spontaneous covariations between brainwide fMRI signals at "rest." We identified two distinct spatial patterns of covariations: one that was amplified and another that was suppressed by catecholamines. Each pattern was associated with the heterogeneous spatial distribution of the expression of distinct catecholamine receptor genes. Our results provide novel insights into the catecholaminergic modulation of large-scale human brain dynamics.


Assuntos
Encéfalo/fisiologia , Catecolaminas/fisiologia , Conectoma , Inibidores da Captação Adrenérgica/farmacologia , Cloridrato de Atomoxetina/farmacologia , Química Encefálica , Estudos Cross-Over , Conjuntos de Dados como Assunto , Método Duplo-Cego , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Receptores de Catecolaminas/análise , Receptores de Catecolaminas/genética , Descanso
11.
ISME J ; 12(11): 2736-2747, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29995838

RESUMO

The microorganisms in the gastrointestinal (GI) tract can influence the metabolism, immunity, and behavior of animal hosts. Increasing evidence suggests that communication between the host and the microbiome also occurs in the opposite direction, with hormones and other host-secreted compounds being sensed by microorganisms. Here, we addressed one key aspect of the host-microbe communication by studying chemotaxis of a model commensal bacterium, Escherichia coli, to several compounds present abundantly in the GI tract, namely catecholamines, thyroid hormones, and polyamines. Our results show that E. coli reacts to five out of ten analyzed chemicals, sensing melatonin, and spermidine as chemorepellents and showing mixed responses to dopamine, norepinephrine and 3,4-dihydroxymandelic acid. The strongest repellent response was observed for the polyamine spermidine, and we demonstrate that this response involves the low-abundance chemoreceptor Trg and the periplasmic binding protein PotD of the spermidine uptake system. The chemotactic effects of the tested compounds apparently correlate with their influence on growth and their stability in the GI tract, pointing to the specificity of the observed behavior. We hypothesize that the repellent responses observed at high concentrations of chemoeffective compounds might enable bacteria to avoid harmful levels of hormones and polyamines in the gut and, more generally, antimicrobial activities of the mucous layer.


Assuntos
Catecolaminas/fisiologia , Quimiotaxia , Escherichia coli/fisiologia , Poliaminas , Hormônios Tireóideos/fisiologia , Proteínas de Escherichia coli/fisiologia , Trato Gastrointestinal/química , Humanos , Proteínas de Membrana/fisiologia , Proteínas de Membrana Transportadoras/fisiologia , Proteínas Periplásmicas de Ligação/fisiologia , Espermidina/metabolismo
12.
PLoS Biol ; 16(2): e2003453, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29420565

RESUMO

The ascending modulatory systems of the brain stem are powerful regulators of global brain state. Disturbances of these systems are implicated in several major neuropsychiatric disorders. Yet, how these systems interact with specific neural computations in the cerebral cortex to shape perception, cognition, and behavior remains poorly understood. Here, we probed into the effect of two such systems, the catecholaminergic (dopaminergic and noradrenergic) and cholinergic systems, on an important aspect of cortical computation: its intrinsic variability. To this end, we combined placebo-controlled pharmacological intervention in humans, recordings of cortical population activity using magnetoencephalography (MEG), and psychophysical measurements of the perception of ambiguous visual input. A low-dose catecholaminergic, but not cholinergic, manipulation altered the rate of spontaneous perceptual fluctuations as well as the temporal structure of "scale-free" population activity of large swaths of the visual and parietal cortices. Computational analyses indicate that both effects were consistent with an increase in excitatory relative to inhibitory activity in the cortical areas underlying visual perceptual inference. We propose that catecholamines regulate the variability of perception and cognition through dynamically changing the cortical excitation-inhibition ratio. The combined readout of fluctuations in perception and cortical activity we established here may prove useful as an efficient and easily accessible marker of altered cortical computation in neuropsychiatric disorders.


Assuntos
Catecolaminas/fisiologia , Córtex Cerebral/fisiologia , Percepção Visual/fisiologia , Inibidores da Captação Adrenérgica/farmacologia , Cloridrato de Atomoxetina/farmacologia , Mapeamento Encefálico , Córtex Cerebral/efeitos dos fármacos , Humanos , Magnetoencefalografia/métodos , Modelos Neurológicos , Estimulação Luminosa , Placebos , Psicofísica
14.
J Assoc Physicians India ; 66(12): 88, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31313563
15.
Memory ; 26(3): 364-376, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28625108

RESUMO

Stressful events have a major impact on memory. They modulate memory formation in a time-dependent manner, closely linked to the temporal profile of action of major stress mediators, in particular catecholamines and glucocorticoids. Shortly after stressor onset, rapidly acting catecholamines and fast, non-genomic glucocorticoid actions direct cognitive resources to the processing and consolidation of the ongoing threat. In parallel, control of memory is biased towards rather rigid systems, promoting habitual forms of memory allowing efficient processing under stress, at the expense of "cognitive" systems supporting memory flexibility and specificity. In this review, we discuss the implications of this shift in the balance of multiple memory systems for the dynamics of the memory trace. Specifically, stress appears to hinder the incorporation of contextual details into the memory trace, to impede the integration of new information into existing knowledge structures, to impair the flexible generalisation across past experiences, and to hamper the modification of memories in light of new information. Delayed, genomic glucocorticoid actions might reverse the control of memory, thus restoring homeostasis and "cognitive" control of memory again.


Assuntos
Memória/fisiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Animais , Encéfalo/fisiologia , Catecolaminas/fisiologia , Glucocorticoides/fisiologia , Humanos
16.
Probiotics Antimicrob Proteins ; 9(3): 215-234, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28229287

RESUMO

This work is concerned with the role of evolutionary conserved substances, neurotransmitters, and neurohormones, within the complex framework of the microbial consortium-immune system-nervous system axis in the human or animal organism. Although the operation of each of these systems per se is relatively well understood, their combined effects on the host organism still await further research. Drawing on recent research on host-produced and microbial low-molecular-weight neurochemicals such as biogenic amines, amino acids, and short-chain fatty acids (SCFAs), we suggest that these mediators form a part of a universal neurochemical "language." It mediates the whole gamut of harmonious and disharmonious interactions between (a) the intestinal microbial consortium, (b) local and systemic immune cells, and (c) the central and peripheral nervous system. Importantly, the ongoing microbiota-host interactivity is bidirectional. We present evidence that a large number of microbially produced low-molecular-weight compounds are identical or homologous to mediators that are synthesized by immune or nervous cells and, therefore, can bind to the corresponding host receptors. In addition, microbial cells specifically respond to host-produced neuromediators/neurohormones because they have adapted to them during the course of many millions of years of microbiota-host coevolution. We emphasize that the terms "microbiota" and "microbial consortium" are to be used in the broadest sense, so as to include, apart from bacteria, also eukaryotic microorganisms. These are exemplified by the mycobiota whose role in the microbial consortium-immune system-nervous system axis researchers are only beginning to elucidate. In light of the above, it is imperative to reform the current strategies of using probiotic microorganisms and their metabolites for treating and preventing dysbiosis-related diseases. The review demonstrates, in the example of novel probiotics (psychobiotics), that many target-oriented probiotic preparations produce important side effects on a wide variety of processes in the host organism. In particular, we should take into account probiotics' capacity to produce mediators that can considerably modify the operation of the microecological, immune, and nervous system of the human organism.


Assuntos
Microbioma Gastrointestinal , Sistema Imunitário/microbiologia , Consórcios Microbianos , Sistema Nervoso/microbiologia , Neurotransmissores/fisiologia , Acetilcolina/fisiologia , Animais , Catecolaminas/fisiologia , Disbiose/microbiologia , Disbiose/prevenção & controle , Ácidos Graxos Voláteis/fisiologia , Histamina/fisiologia , Humanos , Intestinos/microbiologia , Modelos Animais , Probióticos , Serotonina/fisiologia
17.
Behav Brain Res ; 323: 124-132, 2017 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-28153394

RESUMO

Growing evidence suggests that the catecholamine (CA) neurotransmitters dopamine and noradrenaline support hippocampus-mediated learning and memory. However, little is known to date about which forms of hippocampus-mediated spatial learning are modulated by CA signaling in the hippocampus. Therefore, in the current study we examined the effects of 6-hydroxydopamine-induced CA depletion in the dorsal hippocampus on two prominent forms of hippocampus-based spatial learning, that is learning of object-location associations (paired-associates learning) as well as learning and choosing actions based on a representation of the context (place learning). Results show that rats with CA depletion of the dorsal hippocampus were able to learn object-location associations in an automated touch screen paired-associates learning (PAL) task. One possibility to explain this negative result is that object-location learning as tested in the touchscreen PAL task seems to require relatively little hippocampal processing. Results further show that in rats with CA depletion of the dorsal hippocampus the use of a response strategy was facilitated in a T-maze spatial learning task. We suspect that impaired hippocampus CA signaling may attenuate hippocampus-based place learning and favor dorsolateral striatum-based response learning.


Assuntos
Catecolaminas/fisiologia , Hipocampo/fisiologia , Aprendizagem Espacial , Animais , Aprendizagem por Associação/fisiologia , Masculino , Ratos , Aprendizagem Espacial/fisiologia
18.
Subst Use Misuse ; 52(4): 535-547, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28033474

RESUMO

BACKGROUND: There is need for better treatments of addictive behaviors, both substance and non-substance related, termed Reward Deficiency Syndrome (RDS). While the FDA has approved pharmaceuticals under the umbrella term Medication Assisted Treatment (MAT), these drugs are not optimal. OBJECTIVES: It is our contention that these drugs work well in the short-term by blocking dopamine function leading to psychological extinction. However, use of buprenorphine/Naloxone over a long period of time results in unwanted addiction liability, reduced emotional affect, and mood changes including suicidal ideation. METHODS: We are thus proposing a paradigm shift in addiction treatment, with the long-term goal of achieving "Dopamine Homeostasis." While this may be a laudable goal, it is very difficult to achieve. Nevertheless, this commentary briefly reviews past history of developing and subsequently, utilizing a glutaminergic-dopaminergic optimization complex [Kb220Z] shown to be beneficial in at least 20 human clinical trials and in a number of published and unpublished studies. RESULTS: It is our opinion that, while additional required studies could confirm these findings to date, the cited studies are indicative of achieving enhanced resting state functional connectivity, connectivity volume, and possibly, neuroplasticity. Conclusions/Importance: We are proposing a Reward Deficiency Solution System (RDSS) that includes: Genetic Addiction Risk Score (GARS); Comprehensive Analysis of Reported Drugs (CARD); and a glutaminergic-dopaminergic optimization complex (Kb220Z). Continued investigation of this novel strategy may lead to a better-targeted approach in the long-term, causing dopamine regulation by balancing the glutaminergic-dopaminergic pathways. This may potentially change the landscape of treating all addictions leading us to the promised land.


Assuntos
Comportamento Aditivo/fisiopatologia , Catecolaminas/fisiologia , Dopamina/metabolismo , Homeostase , Monoaminoxidase/fisiologia , Neprilisina/fisiologia , Recompensa , Comportamento Aditivo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Homeostase/fisiologia , Humanos , Neuroimagem/métodos , Neurofarmacologia/métodos , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Síndrome
19.
J Physiol ; 595(6): 2129-2146, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27982456

RESUMO

KEY POINTS: Upon repeated application of short ACh pulses to C57BL6J mouse chromaffin cells, the amperometrically monitored secretory responses promptly decayed to a steady-state level of around 25% of the initial response. A subsequent K+ pulse, however, overcame such decay. These data suggest that mouse chromaffin cells have a ready release-vesicle pool that is selectively recruited by the physiological neurotransmitter ACh. The ACh-sensitive vesicle pool is refilled and maintained by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mitochondrial Na+ /Ca2+ exchanger (mNCX). ITH12662, a novel blocker of the mNCX, prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+ ]c clearance. This regulatory pathway may be physiologically relevant in situations of prolonged stressful conflicts where a sustained catecholamine release is regulated by mitochondrial Ca2+ circulation through the mNCX, which couples respiration and ATP synthesis to long-term stimulation of chromaffin cells by endogenously released ACh. ABSTRACT: Using caged-Ca2+ photorelease or paired depolarising pulses in voltage-clamped chromaffin cells (CCs), various pools of secretory vesicles with different readiness to undergo exocytosis have been identified. Whether these pools are present in unclamped CCs challenged with ACh, the physiological neurotransmitter at the splanchnic nerve-CC synapse, is unknown. We have explored here whether an ACh-sensitive ready-release vesicle pool (ASP) is present in C57BL6J mouse chromaffin cells (MCCs). Single cells were fast perfused with a Tyrode solution at 37°C, and challenged with 12 sequential ACh pulses (100 µm, 2 s, every 30 s) plus a K+ pulse given at the end (75 mm K+ ). After the first 2-3 ACh pulses the amperometrically monitored secretory responses promptly decayed to a steady-state level of around 25% of the initial response. The last K+ pulse, however, overcame such decay. Repeated ACh pulses to voltage-clamped cells elicited non-desensitising nicotinic currents. Also, the [Ca2+ ]c transients elicited by repeated ACh pulses that were superimposed on a stable baseline elevation did not undergo decay. The novel blocker of the mitochondrial Na+ /Ca2+ exchanger (mNCX) ITH12662 prevented the decay of secretion elicited by ACh pulses and delayed the rate of [Ca2+ ]c clearance. The experiments are compatible with the idea that C57BL6J MCCs have an ASP vesicle pool that is selectively recruited by the physiological neurotransmitter ACh and is regulated by the rate of Ca2+ delivery from mitochondria to the cytosol, through the mNCX.


Assuntos
Catecolaminas/fisiologia , Células Cromafins/fisiologia , Trocador de Sódio e Cálcio/fisiologia , Acetilcolina/farmacologia , Animais , Cálcio/fisiologia , Células Cultivadas , Células Cromafins/efeitos dos fármacos , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/fisiologia , Potássio/farmacologia
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