RESUMO
BACKGROUND: Galanin (GAL) constitutes a family of neuropeptides composed of four peptides: (i) galanin (GAL), (ii) galanin-message associated peptide (GAMP), (iii) galanin-like peptide (GALP), and (iv) alarin. GAL contains 29/30 amino acids, and its biological action occurs through the interactions with its various receptors (GALR1, GALR2, and GALR3). The neuropeptide GAL regulates several physiological and pathophysiological functions in the central nervous system, the peripheral nervous system, and the peripheral organs. GAL is secreted mainly by oligodendrocytes, astrocytes, and the gastrointestinal tract, and its effect depends on the interaction with its different receptors. These receptors are expressed mainly in the central, peripheral nervous systems and the intestines. OBJECTIVE: The present review evaluates the role of GAL family in inflammatory diseases. An overview is given of the signaling and pharmacological effects due to the interaction between GAL and GALR in different cell types. The potential use of GAL as a therapeutic resource is critically discussed. CONCLUSION: GAL is suggested to have an anti-inflammatory function in some situations and a proinflammatory function in others. The literature on GAL is controversial and currently not conclusive. This could be due to the complexity of the metabolic network signaling induced by the interactions between GAL and GALR. In the next future, GAL might be a promising therapeutic resource for several diseases, but its practical use for disease control is presently not advisable.
Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Galanina/farmacologia , Galanina/uso terapêutico , Doenças do Sistema Nervoso/terapia , Animais , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Receptores de Galanina/fisiologia , Transdução de Sinais/fisiologiaRESUMO
Galanin, a peptide expressed in mammalian brain regions, has been implicated in anxiety and depression. Galanin signalling occurs through three G protein-linked receptors (GAL1, GAL2 and GAL3). Galanin regulates the release of neurotransmitters in some brain regions related to anxiety, including the hippocampus. GAL2 is the most abundant galanin receptor in the dorsal hippocampus. In this study, we evaluated whether galanin administered in the dorsal hippocampus affected anxiety-like behaviours of rats. We also investigated if GAL2 receptors are involved in the anxiogenic-like effect of galanin using a GAL2 antagonist, M871. To achieve these objectives, male adult Wistar rats received intra-dorsal hippocampal delivery of galanin (0.3 and 1.0â¯nmol/0.5⯵l) or vehicle in experiment 1 and GAL2 antagonist M871 (1.0 and 3.0â¯nmol/0.5⯵l) or vehicle in experiment 2. Twenty min after administration of drugs, the animals were tested in the elevated plus-maze (EPM). Galanin (1.0â¯nmol) induced anxiogenic-like behaviours, while the GAL2 receptor antagonist M871 (3.0â¯nmol) induced anxiolytic-like behaviours in rats exposed to the EPM, indicating a tonic effect of galanin. In experiment 3, we evaluated whether previous infusion of the GAL2 antagonist M871 (1 or 2â¯nmol) in the dorsal hippocampus would block the anxiogenic-like effect of galanin in rats tested in the EPM. We showed that M871 (2.0â¯nmol) counteracted the anxiogenic-like effect of galanin infused in the dorsal hippocampus of rats. Altogether, our results provide evidence that galanin promotes pharmacological and tonic anxiogenic-like effects in the dorsal hippocampus, possibly mediated by GAL2 receptors.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Galanina/uso terapêutico , Hipocampo/efeitos dos fármacos , Análise de Variância , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microinjeções , Peptídeos/uso terapêutico , Ratos , Ratos WistarRESUMO
Galanin is a peptide that is present in the central nervous system in mammals, including rodents and humans. The actions of galanin are mediated by three types of metabotropic receptors: GAL1, GAL2, and GAL3. GAL1 and GAL3 increase K(+) efflux, and GAL2 increases intracellular Ca(2+) levels. The distribution of galanin and its receptors suggests its involvement in fear and/or anxiety. The periaqueductal gray matter (PAG) is a key mediator of defensive behaviors that is both targeted by galaninergic projections and supplied with GAL1 receptors and, less markedly, GAL2 receptors. We examined the effects of galanin microinjections in the dorsal PAG (dPAG) on the performance of rats in different models of anxiety. Male Wistar rats (n=7-12) were implanted with guide cannulae in the dPAG. They received microinjections of either galanin (0.3, 1.0, and 3.0 nmol) or vehicle and were tested in the Vogel conflict test (VCT), elevated plus maze (EPM), and elevated T-maze (ETM). Rats that were tested in the ETM were further evaluated for exploratory activity in the open field test (OFT). Galanin microinjections had no effects on anxiety-like behavior in the EPM or VCT or exploratory activity in the EPM or OFT. In the ETM, however, microinjections of 3 nmol galanin impaired learned anxiety (i.e., avoidance of the open arms) without changing unconditioned fear (i.e., escape from the open arms). The present data suggest that galanin transmission in the dPAG inhibits the acquisition of anxiety-like responses in the ETM.
Assuntos
Ansiedade/tratamento farmacológico , Galanina/farmacologia , Galanina/uso terapêutico , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Animais , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Aprendizagem da Esquiva/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Microinjeções , Substância Cinzenta Periaquedutal/fisiologia , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
Galanin and 5-HT coexist in dorsal raphe nucleus (DRN) neurons. Microinjection of galanin into the DRN reduces the firing rate of serotonin neurons. Serotonergic neurons projecting from the DRN to the amygdala facilitate learned anxiety producing an anxiogenic effect, while those projecting from the periaqueductal grey affect innate anxiety producing a panicolytic effect. We tested the hypothesis that injection of galanin into rat DRN would induce anxiolytic/panicogenic effects in the elevated T-maze (ETM), a model that allows for the evaluation of both of these effects. Galanin infusion into the mid-caudal DRN, but not into the rostral DRN, impaired inhibitory avoidance, suggesting an anxiolytic effect. The effective dose of galanin (0.3 nmol) did not modify locomotor activity in the open field. Contrary to expectations, microinjection of galanin into the DRN did not facilitate the latency of one-way escape in the ETM. Pretreatment with a galanin antagonist, M40, attenuated galanin-induced impairment of inhibitory avoidance. The results show that microinjection of a low dose of galanin only into the mid-caudal DRN has an anxiolytic effect. This effect seems to be mediated, at least in part, by galanin receptors. Further investigation is necessary to identify the receptor subtypes and the DRN subregion involved in the anxiolytic effect of galanin.