Note:

A stanniocalcina-1 (STC1) é uma glicoproteína caracterizada como um fator endócrino com ação anti-hipercalcêmica/hipocalcêmica originalmente descoberta em peixes. Em mamíferos, esse hormônio está expresso em praticamente todos os tecidos, regula diversas funções biológicas e atua como um fator autócrino/ parácrino. Diversas evidências demonstram o envolvimento da STC1 no desenvolvimento ósseo. Durante a embriogênese, a STC1 é expressa nos primeiros estágios de condensação mesenquimal e, posteriormente, se mantém restrita a preosteoblastos e osteoblastos maduros. Além disso, a STC1 estimula a mineralização óssea através do aumento da expressão de transportadores de fosfato e da osteopontina, uma sialoglicoproteína que atua na mineralização óssea. Células-tronco adultas simbolizam atualmente a fonte mais acessível de células progenitoras utilizadas em terapias celulares e engenharia de tecidos. O tecido adiposo contém uma população de células biológica e clinicamente interessantes denominada células tronco adiposo derivadas (CTADs). Atualmente as CTADs são a melhor fonte de células tronco adultas podendo ser obtidas através de procedimentos minimamente invasivos. Um grande número de estudos têm demonstrado o potencial osteogênico dessas células, no entanto, ainda é um desafio a compreensão dos mecanismos envolvidos na diferenciação osteogênica a partir das CTADs. Neste estudo, foi demonstrado que sete dias de indução osteogênica das CTADs na presença de 50 ng/mL de STC1 aumentaram significativamente a expressão gênica e proteica dos marcadores osteogênicos: fosfatase alcalina (FA), runt related gene 2 (RUNX2) e osteopontina (OPN) O aumento na atividade da enzima FAS foi relacionado diretamente com a maior expressão gênica e proteica. Além disso, a STC1 modula a via de sinalização pAKt/pGSK3-β/βcatenina em preosteoblastos de 7 dias sugerindo que seus efeitos sobre a osteogênese sejam mediados por essa via de sinalização. O peptídeo neuroendócrino CGRP (peptídeo relacionado ao gene da calcitonina) possui similaridades com STC1 e desempenha um importante papel nas fases iniciais da diferenciação dos osteoblastos. O CGRP ativa o receptor CALCRL, formando um dímero com a proteína transmembrana acessória RAMP1. Para elucidar o envolvimento da STC1 nas vias de sinalização relacionadas a receptores de calcitonina foi investigado o efeito desse hormônio na modulação 8 do receptor do CGRP e receptor de calcitonina (CTR) em CTADs diferenciadas para preosteoblastos e células Hek 293 superexpressoras de CALCRL/RAMP1 e CTR. A STC1 não alterou a expressão dos genes CALCRL e ramp1 durante a osteoblastogênese mas provocou alterações na distribuição espacial do complexo CALCRL/RAMP1 na membrana plasmática de preosteoblastos, induzindo a formação de clusters Além do efeito sobre a sinalização do CGRP a STC1 demonstrou inibir a sinalização da calcitonina diminuindo a produção de cAMP em células transfectadas com CTR. A STC1 não alterou os níveis intracelulares de cálcio e ATP. Esses resultados indicam que, embora não atue diretamente via os receptores CALCRL/RAMP1 e CTR, a STC1 modula a sinalização dos peptídeos CGRP e CT. Estudos mais detalhados sobre os efeitos da STC1 nas diferentes vias de sinalização são necessários para desvendar completamente os mecanismos de diferenciação osteogênicos das CTADs estimuladas por esse hormônio. / The stanniocalcin-1 (STC1) is a glycoprotein characterized as an endocrine factor with anti-hypercalcemic / hypocalcemic action, originally identified in fish. The hormone in mammals is expressed in virtually all tissues and regulates diverse biological functions, acting as an autocrine / paracrine factor. Many evidences demonstrate that STC1 is able to regulate bone development. During embryogenesis the STC1 is expressed in early stages of mesenchymal condensation and thereafter remains restricted to preosteoblast and mature osteoblast. Furthermore, STC1 stimulates bone mineralization by increasing the phosphate transporter expression and osteopontin, a sialoglycoprotein involved in bone mineralization. Adult stem cells currently symbolize the most accessible source of stem cells used in cell therapy and tissue engineering. Adipose tissue contains a population of biological cells clinically interesting called adipose derived stem cells (ASC). Currently, the ASCs are the best source of adult stem cells and can be harvested using minimally invasive procedures. A large number of studies had shown osteogenic potential of these cells, however, it is still a challenge to understand the mechanisms involved in osteogenic differentiation from ASCs This study demonstrated that 7-day preosteoblast in the presence of 50 ng / ml STC1 significantly increased gene and protein expression of osteogenic markers: alkaline phosphatase (ALP), runt related gene 2 (RUNX2), and osteopontin (OPN ). Also, there was an increase in the enzymatic activity of the ALP, possibly related to both gene and protein expression. Furthermore, STC1 modulates pAkt / pGSK3-β / βcatenina signaling in 7-day preosteoblast, suggesting that the STC1 effects on the osteogenesis is mediated by this pathway. The neuroendocrine peptide CGRP (calcitonin gene related peptide) has similarities to STC1 and plays an important role in the early stages of osteoblast differentiation. The active CGRP receptor form a dimer with the receptor activity-modifying protein 1 (RAMP1). To elucidate the involvement of STC1 in signaling pathways related to calcitonin receptors, it was investigated the STC1 effect on peptide receptor modulating the calcitonin gene related peptide (CGRP) and the calcitonin receptor (CTR) in 7-day preosteoblast, and in Hek 293 cells transfected with CALCRL / RAMP1 and CTR The STC1 did not change the expression of genes CALCRL and ramp1 during osteoblastogenesis but modified the plasma membrane spatial distribution of 10 CALCRL/RAMP1 in preosteoblast. Besides the effect on CGRP signaling, STC1 inhibited the calcitonin signaling by decreasing cAMP production in cells transfected with CTR. The STC1 did not alter intracellular calcium levels and ATP. These results indicated that STC1 does not act on the same receptors for calcitonin and CGRP, but modulates the action of these peptides. Studies on the effects of STC1 in different signaling pathways are necessary for understanding the mechanisms underlying the STC1 ability in enhancing osteoblastogenesis from hASCs.

This thesis explores physiological changes occurring after acute brain injury. The first two chapters focus on traumatic brain injury (TBI), a significant cause of disability and death worldwide. I discuss the evidence behind current management of secondary brain injury with emphasis on partial brain oxygen tension (PbtO2) and intracranial pressure (ICP). The second chapter describes a subgroup analysis of the effect of hypothermia on ICP and PbtO2 in 17 patients enrolled to the Eurotherm3235 trial. There was a mean decrease in ICP of 4.1 mmHg (n=9, p < 0.02) and a mean decrease in PbtO2 (7.8 ± 3.1 mmHg (p < 0.05)) in the hypothermia group that was not present in controls. The findings support previous studies in demonstrating a decrease in ICP with hypothermia. Decreased PbtO2 could partially explain worse outcomes seen in the hypothermia group in the Eurotherm3235 trial. Further analysis of PbtO2 and ICP guided treatment is needed. The third chapter focuses on delayed cerebral ischaemia (DCI) after aneurysmal subarachnoid haemorrhage (aSAH), another form of acute brain injury that causes significant morbidity and mortality. I include a background of alpha-calcitonin gene-related peptide (αCGRP), a potential treatment of DCI, along with results from a systematic review and meta-analysis of nine experimental models investigating αCGRP. The meta-analysis demonstrates a 40.8 ± 8.2% increase in cerebral vessel diameter in those animals treated with αCGRP compared with controls (p < 0.0005, 95% CI 23.7 to 57.9). Neurobehavioural scores were reported in four publications and showed a Physiological responses to brain tissue hypoxia and blood flow after acute brain injury standardised mean difference of 1.31 in favour of αCGRP (CI -0.49 to 3.12). I conclude that αCGRP reduces cerebral vessel narrowing seen after SAH in animal studies but note that there is insufficient evidence to determine its effect on functional outcomes. A review of previous trials of αCGRP administration in humans is included, in addition to an original retrospective analysis of CSF concentrations of αCGRP in humans. Enzyme-linked immunosorbent assay of CSF (n = 22) was unable to detect αCGRP in any sample, which contrasts with previous studies and was likely secondary to study methodology. Finally, I summarise by discussing a protocol I designed for a dose-toxicity study involving the intraventricular administration of αCGRP to patients with aSAH and provide some recommendations for future research. This protocol was based upon the systematic review and was submitted to the Medical Research Council's DPFS funding stream during the PhD.

Peptide hormones are responsible for cellular functions critical to the survival of an organism. Approximately 50% of all known peptide hormones are post-translationally modified at the C-terminus. Enzymatic oxidative conversion of C-terminal glycine extended peptide precursors results in an a-amidated peptide and glyoxylate. Peptidylglycine a-amidating monooxygenase (PAM) is the single known enzyme responsible for catalyzing this reaction. PAM is an O2, Cu(II), and Zn(II) dependent bifunctional enzyme. Initially, PAM hydroxylates the glycyl a-carbon followed by dealkylation of the hydroxylated intermediate to an a-amidated product and glyoxylate. PAM is also responsible for the conversion of glycine extended fatty acids to fatty acid amides and glyoxylate. PAM catalyzes the activation of all glycine-extended prohormones including biomolecules ranging from neuro to physio-homeostatic hormones. Identification of a-amidated hormones from a biological source has been severely hindered by the lack of a specific assay for this distinctive class of biological hormones, indicating that numerous a-amidated hormones remain undiscovered. Based on the selective in situ chemistry of PAM, a novel and specific assay was developed for the discovery of a-amidated hormones. The identification of novel a-amidated hormones will lead to an increased understanding of post-translational modifications and will pioneer a new understanding of a-amidated hormone biosynthesis, regulation, and bioactivity. Discovery of novel a-amidated biomolecules could also lead to their use as pharmaceuticals as there are several currently marketed a-amidated peptide based pharmaceuticals.Inhibition of PAM in cell culture leads to the accumulation of glycine-extended hormones in the conditioned medium. The medium was fractionated by chromatographic techniques and each specific fraction was then assayed by the newly developed platform technology for the presence of a-amidated hormones. For every a-amidated hormone synthesized by PAM, glyoxylate is also formed. Based on this 1:1 molar ratio, several novel spectrophotometric, fluorescent, and chemi-luminescent enzyme linked assays for glyoxylate were developed, which when utilized on cell culture fractions proved positive for the identification of a-amidated hormones. Each novel spectroscopic assay was independently verified by a variety of known methodologies. Moreover the assay was utilized to identify two known a-amidated hormones accumulated from cell culture, which were further verified by Mass Spectral analysis.

Neuropeptides are present in nerve fibers of the upper and lower airways. Local release of these substances may be of importance for the pathophysiology of airway disorders and may play a role in responses to different stimuli. However, little is known about the distribution of neuropeptides in the larynx. The superior laryngeal nerve is one of the vagal branches supplying the larynx. The aim of the present study was to investigate the fiber composition of this nerve and to analyse the distribution of different neuropeptides and mast cells in the larynx. The internal and the external branches of the superior laryngeal nerve had a similar number and size of the nerve fibers. Numerous unmyelinated fibers were evenly distributed in the branches. A large majority of the fibers were sensory myelinated and unmyelinated fibers; only a few of the myelinated fibers of the external branch ( 2-10 %) were motor. About a quarter of the unmyelinated fibers of the internal and the external branches had their cell bodies in the brainstem, and single myelinated and unmyelinated fibers emanated from the superior cervical ganglion. In every superior laryngeal nerve examined one to three spherical paraganglia were observed. These paraganglia contained cells which were similar to the type I and type II cells found in the carotid body and the paraganglia of the recurrent laryngeal nerve. Thin-walled sinusoidal blood vessels which were sometimes fenestrated were also present The laryngeal mucosa was supplied with nerve fibers exhibiting substance P- and calcitonin gene-related peptide-like immunoreactivity with regional differences in the distribution. The laryngeal side of the epiglottis and the ventral recess were richly supplied, and the vocal cords showed no evidence of immunoreactive nerve fibers. The distribution of connective tissue mast cells and mucosal mast cells/globular leucocytes was similar to that of nerve fibers displaying substance P- and calcitonin gene-related peptide-like immunoreactivity. These cells were found in close approximation to nerve fibers. Acetylcholinesterase-positive ganglionic cells in the larynx showed vasoactive intestinal polypeptide-, neuropeptide Y-and enkephalin-like immunoreactivity. Neuropeptide Y-like immunoreactivity was co-localized with tyrosine-hydroxylase/dopamine beta-hydroxylase-like immunoreactivity in nerve fibers in some blood vessel walls. Enkephalin-like immunoreactivity was rarely found in this location and co-localization with tyrosine- hydroxylase-like immunoreactivity was not detected. In glands and some blood vessel walls neuropeptide Y- and enkephalin-like immunoreactivity were localized in nerve fibers showing a positive acetylcholinesterase reaction and vasoactive intestinal polypeptide-like immunoreactivity. Thus, this indicates that neuropeptide Y is present in both the sympathetic and parasympathetic nervous systems, while enkephalin and vasoactive intestinal polypeptide are confined to the parasympathetic nervous system in the rat larynx. The present study shows that the superior laryngeal nerve is mainly sensory, and the study also provides a morphological basis for neuropeptide effects in laryngeal physiology/pathophysiology. / <p>S. 1-27: sammanfattning, s. 29-97: 6 uppsatser</p> / digitalisering@umu

G protein-coupled receptors (GPCRs) are composed of seven transmembrane domains and play an essential role in regulating physiological functions and mediating responses to environmental stimuli, biogenic amines, neurotransmitters, peptides, lipids, and hormones. The calcitonin-like diuretic hormone 31 (DH31) is known to elicit natriuresis from the Malpighian tubules (MTs) of mosquitoes Anopheles gambiae and Aedes aegypti upon blood feeding. However, the contribution of DH31 cognate receptor, calcitonin receptor 1 (GPRCAL1), has not been evaluated with respect to postprandial fluid regulation or myostimulatory activity in blood feeding insects. Thus, this dissertation has investigated potential roles of AedaeGPRCAL1 in the regulation of fluid homeostasis and hindgut muscle contraction in female A. aegypti mosquito. The full length cDNA encoding AedaeGPRCAL1 was cloned and sequenced. The receptor expression in the MTs and hindgut from female mosquito was analyzed by western blot and immunohistochemistry using anti-AedaeGPRCAL1 affinity purified antibodies, and subsequently its role in fluid transport and hindgut contraction was evaluated by RNA interference (RNAi). The mosquitoes that underwent knock-down of the AedaeGPRcal1 exhibited up to 57% lower rate of MT fluid secretion in presence of Aedae-DH31 in the in vitro assay and a ~30% reduction in the fluid excreted from live females upon blood feeding. The receptor was immunolocalized in principal cells, predominantly towards the distal end of MTs. Analyses of receptor signal probability indicate the receptor is expressed in a gradient-like fashion along the length of the MTs. A striking discovery was the fact that not all principal cells express the receptor, contrary to previous belief. Immunolocalization revealed the AedaeGPRCAL1 is expressed in hindgut circular and longitudinal muscles. The application of DH31 increased the frequency of hindgut contractions in all female mosquitoes, those injected with AedaeGPRcal1 dsRNA and controls, as compared to their basal contraction rate, but the percent change in frequency of hindgut contraction from AedaeGPRcal1 knock-down females was about 2-fold lower than the controls after application of Aedae-DH31. To my knowledge, this is first evidence of RNAi-induced phenotypes in any invertebrate that allowed the quantification of the contribution of single family B GPCR to fluid loss and muscle contractility.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Linköping : Univ., 2002. / Härtill 4 uppsatser.

Submitted by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-23T13:14:13Z No. of bitstreams: 1 Publico-NOVO-05.pdf: 1218530 bytes, checksum: 4ed86e26ba531f290cfc9a29f57fba4d (MD5) / Approved for entry into archive by Maria Anália Conceição (marianaliaconceicao@gmail.com) on 2016-06-23T13:15:03Z (GMT) No. of bitstreams: 1 Publico-NOVO-05.pdf: 1218530 bytes, checksum: 4ed86e26ba531f290cfc9a29f57fba4d (MD5) / Made available in DSpace on 2016-06-23T13:15:03Z (GMT). No. of bitstreams: 1 Publico-NOVO-05.pdf: 1218530 bytes, checksum: 4ed86e26ba531f290cfc9a29f57fba4d (MD5) Previous issue date: 2014 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Introdução: A disfunção na liberação de neuropeptídeos acarreta alterações na pele, podendo gerar distúrbios no processo cicatricial e/ou afecções cutâneas. Sendo assim, a liberação de neuropeptídeos é estudada na literatura, relacionando a utilização de agentes eletrofísicos. Objetivo: Investigar o efeito da estimulação elétrica na liberação de neuropeptídeos SP e CGRP em pele de ratos. Métodos: Foram utilizados 28 animais distribuídos em 4 grupos, Grupo Controle (GC): as amostras foram coletadas após 60 minutos da tricotomia sem estímulo elétrico; Grupo Sham (GS): após 60min da tricotomia foram colocadas as placas de eletrodos com esponja umedecida com cloreto de sódio 0,9% e sobreposto na linha mediana dorsal e dispersivo na região ventral, com o aparelho desligado por 30minutos; Grupo Estimulação Elétrica com Polo Positivo (GPP): após 60 minutos da tricotomia, foi realizada a estimulação elétrica sobre a linha mediana dorsal com polaridade Positiva e o no Grupo Estimulação Elétrica com polaridade Negativa (GPN): os mesmos parâmetros utilizados acima, com a mudança, onde o polo negativo passou para linha mediana dorsal. Ao término da estimulação elétrica, foram coletadas amostras de pele, submetidas ao Western blotting para análise dos neuropeptídeos CGRP e SP. Para a análise estatística foi utilizado o teste de Análise Variância (ANOVA) para identificar a diferença entre os grupos. Resultado: Não causou diferença significante na liberação de CGRP e SP na pele de rato. Conclusão: A estimulação elétrica ultraexcitante não influenciou na liberação de neuropeptídeos, CGRP e SP, em pele de ratos. / Introduction: A dysfunction in the release of neuropeptides cause changes in the skin, and may cause disturbances in the healing process and/or skin disorders. Therefore the release of neuropeptides has been studied in the literature, connecting the use of electrophysical agents. Objective: To investigate the effect of electrical stimulation on the release of neuropeptides SP and CGRP in rat skin. Methods: 28 animals were randomly divided into 4 groups, Control Group (CG): the samples were collected 60 minutes after shaving without electrical stimulation; Sham Group (SG): after 60 minutes of trichotomy were placed electrodes plates with damp sponge with sodium chloride 0.9% and superimposed on the dorsal midline and dispersive on the ventral region, with the equipment off for 30 minutes; Electrical Stimulation Positive Pole Group (GPP): later 60 minutes of trichotomy, electrical stimulation was performed on the dorsal midline with positive polarity and the Electrical Stimulation Group with negative polarity (NPG): the same parameters used above, with the change where the negative pole was passed into the dorsal midline. At the end of electrical stimulation, skin samples, tested by Western Blotting for analysis of neuropeptides CGRP and SP, were collected. For statistical analysis, analysis of variance (ANOVA) was used to identify differences between the groups. Result: There was a minor release of neuropeptides from the negative and positive polarity, however, not significant. Conclusion: The ultra-exciting electrical stimulation did not influence the release of neuropeptides, SP and CGRP, in rat skin.

A stanniocalcina-1 (STC1) é uma glicoproteína caracterizada como um fator endócrino com ação anti-hipercalcêmica/hipocalcêmica originalmente descoberta em peixes. Em mamíferos, esse hormônio está expresso em praticamente todos os tecidos, regula diversas funções biológicas e atua como um fator autócrino/ parácrino. Diversas evidências demonstram o envolvimento da STC1 no desenvolvimento ósseo. Durante a embriogênese, a STC1 é expressa nos primeiros estágios de condensação mesenquimal e, posteriormente, se mantém restrita a preosteoblastos e osteoblastos maduros. Além disso, a STC1 estimula a mineralização óssea através do aumento da expressão de transportadores de fosfato e da osteopontina, uma sialoglicoproteína que atua na mineralização óssea. Células-tronco adultas simbolizam atualmente a fonte mais acessível de células progenitoras utilizadas em terapias celulares e engenharia de tecidos. O tecido adiposo contém uma população de células biológica e clinicamente interessantes denominada células tronco adiposo derivadas (CTADs). Atualmente as CTADs são a melhor fonte de células tronco adultas podendo ser obtidas através de procedimentos minimamente invasivos. Um grande número de estudos têm demonstrado o potencial osteogênico dessas células, no entanto, ainda é um desafio a compreensão dos mecanismos envolvidos na diferenciação osteogênica a partir das CTADs. Neste estudo, foi demonstrado que sete dias de indução osteogênica das CTADs na presença de 50 ng/mL de STC1 aumentaram significativamente a expressão gênica e proteica dos marcadores osteogênicos: fosfatase alcalina (FA), runt related gene 2 (RUNX2) e osteopontina (OPN) O aumento na atividade da enzima FAS foi relacionado diretamente com a maior expressão gênica e proteica. Além disso, a STC1 modula a via de sinalização pAKt/pGSK3-β/βcatenina em preosteoblastos de 7 dias sugerindo que seus efeitos sobre a osteogênese sejam mediados por essa via de sinalização. O peptídeo neuroendócrino CGRP (peptídeo relacionado ao gene da calcitonina) possui similaridades com STC1 e desempenha um importante papel nas fases iniciais da diferenciação dos osteoblastos. O CGRP ativa o receptor CALCRL, formando um dímero com a proteína transmembrana acessória RAMP1. Para elucidar o envolvimento da STC1 nas vias de sinalização relacionadas a receptores de calcitonina foi investigado o efeito desse hormônio na modulação 8 do receptor do CGRP e receptor de calcitonina (CTR) em CTADs diferenciadas para preosteoblastos e células Hek 293 superexpressoras de CALCRL/RAMP1 e CTR. A STC1 não alterou a expressão dos genes CALCRL e ramp1 durante a osteoblastogênese mas provocou alterações na distribuição espacial do complexo CALCRL/RAMP1 na membrana plasmática de preosteoblastos, induzindo a formação de clusters Além do efeito sobre a sinalização do CGRP a STC1 demonstrou inibir a sinalização da calcitonina diminuindo a produção de cAMP em células transfectadas com CTR. A STC1 não alterou os níveis intracelulares de cálcio e ATP. Esses resultados indicam que, embora não atue diretamente via os receptores CALCRL/RAMP1 e CTR, a STC1 modula a sinalização dos peptídeos CGRP e CT. Estudos mais detalhados sobre os efeitos da STC1 nas diferentes vias de sinalização são necessários para desvendar completamente os mecanismos de diferenciação osteogênicos das CTADs estimuladas por esse hormônio. / The stanniocalcin-1 (STC1) is a glycoprotein characterized as an endocrine factor with anti-hypercalcemic / hypocalcemic action, originally identified in fish. The hormone in mammals is expressed in virtually all tissues and regulates diverse biological functions, acting as an autocrine / paracrine factor. Many evidences demonstrate that STC1 is able to regulate bone development. During embryogenesis the STC1 is expressed in early stages of mesenchymal condensation and thereafter remains restricted to preosteoblast and mature osteoblast. Furthermore, STC1 stimulates bone mineralization by increasing the phosphate transporter expression and osteopontin, a sialoglycoprotein involved in bone mineralization. Adult stem cells currently symbolize the most accessible source of stem cells used in cell therapy and tissue engineering. Adipose tissue contains a population of biological cells clinically interesting called adipose derived stem cells (ASC). Currently, the ASCs are the best source of adult stem cells and can be harvested using minimally invasive procedures. A large number of studies had shown osteogenic potential of these cells, however, it is still a challenge to understand the mechanisms involved in osteogenic differentiation from ASCs This study demonstrated that 7-day preosteoblast in the presence of 50 ng / ml STC1 significantly increased gene and protein expression of osteogenic markers: alkaline phosphatase (ALP), runt related gene 2 (RUNX2), and osteopontin (OPN ). Also, there was an increase in the enzymatic activity of the ALP, possibly related to both gene and protein expression. Furthermore, STC1 modulates pAkt / pGSK3-β / βcatenina signaling in 7-day preosteoblast, suggesting that the STC1 effects on the osteogenesis is mediated by this pathway. The neuroendocrine peptide CGRP (calcitonin gene related peptide) has similarities to STC1 and plays an important role in the early stages of osteoblast differentiation. The active CGRP receptor form a dimer with the receptor activity-modifying protein 1 (RAMP1). To elucidate the involvement of STC1 in signaling pathways related to calcitonin receptors, it was investigated the STC1 effect on peptide receptor modulating the calcitonin gene related peptide (CGRP) and the calcitonin receptor (CTR) in 7-day preosteoblast, and in Hek 293 cells transfected with CALCRL / RAMP1 and CTR The STC1 did not change the expression of genes CALCRL and ramp1 during osteoblastogenesis but modified the plasma membrane spatial distribution of 10 CALCRL/RAMP1 in preosteoblast. Besides the effect on CGRP signaling, STC1 inhibited the calcitonin signaling by decreasing cAMP production in cells transfected with CTR. The STC1 did not alter intracellular calcium levels and ATP. These results indicated that STC1 does not act on the same receptors for calcitonin and CGRP, but modulates the action of these peptides. Studies on the effects of STC1 in different signaling pathways are necessary for understanding the mechanisms underlying the STC1 ability in enhancing osteoblastogenesis from hASCs.