The neuropeptide galanin (GAL) is widely distributed in the central and peripheral nervous systems. It is a modulator of various physiological and pathological processes, and it mediates its effects via three G protein-coupled receptors (GAL 1-3 receptors). A role for GAL as a modulator of mood and anxiety was suggested, because GAL and its receptors are highly expressed in limbic brain structures of rodents. In recent years, numerous studies of animal models have suggested an involvement of GAL and GAL 1 and GAL 2 receptors in anxiety-and depression-related behavior. However, to date, there is sparse literature implicating GAL 3 receptors in behavioral functions. Therefore, we studied the behavior of GAL 3 receptor-deficient (GAL 3 -KO) mice to elucidate whether GAL 3 receptors are involved in mediating behavior-associated actions of GAL. The GAL 3 -KO mouse line exhibited normal breeding and physical development. In addition to behavioral tests, phenotypic characterization included analysis of hematology, amino acid profiles, metabolism, and sudomotor function. In contrast to WT littermates, male GAL 3 -KO mice exhibited an anxietylike phenotype in the elevated plus maze, open field, and light/ dark box tests, and they were less socially affiliated than WT animals to a stranger mouse in a social interaction test. In conclusion, our data suggest involvement of GAL 3 receptors in GAL-mediated effects on mood, anxiety, and behavior, making it a possible target for alternative treatment strategies for mood disorders.T hirty years ago, Tatemoto et al. (1) isolated the neuropeptide galanin (GAL), a 29-aa (30-aa in humans) peptide, from porcine intestine. The peptide is highly conserved throughout evolution and found in many other species. GAL is widely distributed in the CNS and peripheral nervous system, and it has a variety of biological and physiological functions, ranging from energy homeostasis, reproduction, and feeding to cognition and learning (2). In the murine brain, GAL mRNA is extensively expressed in the hypothalamic and brainstem areas. The highest expression levels were observed in the preoptic, periventricular, and dorsomedial hypothalamic nuclei; bed nucleus of the stria terminalis (BNST); medial and lateral amygdala; locus coeruleus; and nucleus of the solitary tract (3). Furthermore, GAL coexists with the serotonin and norepinephrine systems in the rodent brain and acts as an inhibitory neuromodulator of norepinephrine, serotonin, dopamine, glutamate, and acetylcholine function (4). The expression pattern and neuromodulatory functions of GAL suggest a role for this neuropeptide in mood disorders like anxiety and depression. Accordingly, administration of GAL via the intracerebroventricular (i.c.v.) route or into the dopaminergic ventral tegmental area induced depression-like behavior in the rat forced swim test (FST) (5, 6). Several studies in GAL-overexpressing transgenic mice reported an increased depression-like behavior in the FST (7, 8) but found no differences in anxiety-related behavior und...
The neuropeptide galanin has been ascribed different roles in modulating physiological functions in the skin. The present study examined the function of galanin in eccrine sweat gland physiology. We demonstrated secretion of galanin by sweat glands in vivo by radioimmunoassay of human sweat (20-192 fmol galanin/ml). Furthermore, human sweat glands expressed galanin receptors GalR2 and GalR3. Using chamber short-circuit current (Isc) measurements showed that application of galanin to human NCL-SG3 cells led to a significant increase in Isc, which was inhibited by the presence of chloride channel blockers and in chloride-free Krebs solution. Additionally, application of SNAP 37889, a non-peptidergic selective antagonist of GalR3, abolished the effect of galanin on Isc. In summary, our results show that galanin can regulate transepithelial chloride ion transport and fluid secretion by stimulating GalR3 in NCL-SG3 cells and demonstrate a possible important extraneural function of galanin in sweat gland physiology.
Antimicrobial peptides (AMPs) could represent promising therapeutic agents against fungal pathogens, especially in cases of pathogen resistance to common antifungal substances. The neuropeptides galanin message-associated peptide (GMAP) and neuropeptide Y (NPY) are both potent AMPs against certain microbes. The objective of this study was to test clinically relevant non-albicans Candida strains (C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. pelliculosa, C. tropicalis and C. utilis) with regard to their susceptibilities to NPY and GMAP. GMAP showed a higher potency than NPY, which only inhibited growth of some isolates of C. krusei, C. tropicalis and C. utilis. Interestingly, the fluconazole-resistant C. krusei was susceptible to both AMPs. In summary, we show that these neuropeptides have Candida strain-dependent antifungal activity, which in some cases does not match the susceptibility of the strains to the positive controls fluconazole and magainin I. Thus, the findings demonstrate the therapeutic potential of these AMPs in cases of resistance to traditional antifungal substances. This study also confirms the research on neuropeptides as potential fungicides, which are still in the early stages. The results also suggest that testing of strain-specific susceptibility is mandatory.
The neuropeptide galanin is distributed in the central and peripheral nervous systems and in non-neuronal peripheral organs, including the skin. Galanin acts via three G protein-coupled receptors which, except galanin receptor 1, are expressed in various skin structures. The galanin system has been associated with inflammatory processes of the skin and of several other organs. Psoriasis is an inflammatory skin disease with increased neovascularization, keratinocyte hyperproliferation, a proinflammatory cytokine milieu, and immune cell infiltration. In this study, we showed that galanin receptor 3 is present in endothelial cells in human and murine dermal vessels and is co-expressed with nestin in neo-vessels of psoriatic patients. Moreover, in a murine psoriasis model, we showed that C57/BL6 mice lacking galanin receptor 3 display a milder course of psoriasis upon imiquimod treatment, leading to decreased disease severity, delayed neo-vascularization, reduced infiltration of neutrophils, and significantly lower levels of proinflammatory cytokines compared with wild-type mice. In contrast, galanin receptor 2-knockout animals did not differ significantly from wild type mice at both the macroscopic and molecular levels in their inflammatory response to imiquimod treatment. Our data indicate that galanin receptor 3, but not galanin receptor 2, plays an important role in psoriasis-like skin inflammation.
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