Pub Date : 2014-11-01DOI: 10.1016/j.regpep.2014.11.005
Manyi Sun , Feng Wang , Ping Feng
Cellular apoptosis and colonic dysmotility are involved in diabetes mellitus (DM) complications. Insulin-like growth factor-1 (IGF-1) is known to affect apoptosis and proliferation. Here, we demonstrated that the treatment of 1500 ng/kg IGF-1 partly recovers the decrease of the muscle thickness, body weight and gastrointestinal transit rate in DM rats. The gastrointestinal transit rate is positively correlated with the IGF-I level, but negatively correlated with the level of colonic cellular apoptosis. The DM-induced colonic apoptosis is also attenuated by the IGF-1 stimulation. Moreover, IGF-1 inhibits the apoptosis of the isolated colonic SMCs in vitro via the activation of PI3K/Akt and ERK1/2 signaling pathways. Taken together, our data indicated that IGF-1 inhibits the DM-induced colonic SMC apoptosis and might be involved in the alleviation of colonic dysmotility in diabetic rats.
{"title":"Insulin-like growth factor-1 inhibits colonic smooth muscle cell apoptosis in diabetic rats with colonic dysmotility","authors":"Manyi Sun , Feng Wang , Ping Feng","doi":"10.1016/j.regpep.2014.11.005","DOIUrl":"10.1016/j.regpep.2014.11.005","url":null,"abstract":"<div><p>Cellular apoptosis and colonic dysmotility are involved in diabetes mellitus (DM) complications. Insulin-like growth factor-1 (IGF-1) is known to affect apoptosis and proliferation. Here, we demonstrated that the treatment of 1500<!--> <span><span>ng/kg IGF-1 partly recovers the decrease of the muscle thickness, body weight and gastrointestinal transit rate in DM rats. The gastrointestinal transit rate is positively correlated with the IGF-I level, but negatively correlated with the level of colonic cellular apoptosis. The DM-induced colonic apoptosis is also attenuated by the IGF-1 stimulation. Moreover, IGF-1 inhibits the apoptosis of the isolated colonic SMCs in vitro via the activation of PI3K/Akt and ERK1/2 </span>signaling pathways. Taken together, our data indicated that IGF-1 inhibits the DM-induced colonic SMC apoptosis and might be involved in the alleviation of colonic dysmotility in diabetic rats.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"194 ","pages":"Pages 41-48"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.11.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32860979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Galanin is a neuropeptide expressed in the central and peripheral nervous systems. Galanin is known to be biosynthesized in neural and endocrine cells, but little evidence exists for its synthesis in other cells. In this study, we explored galanin-releasing nonneural cells using radioimmunoassay, finding that some fibroblasts produced and released the galanin-like immunoreactive component (galanin-LI). The molecular weight of the galanin-LI obtained from the fibroblasts, as measured by gel filtration chromatography and Western blotting, was 14kDa and suggested that the compound was progalanin. Peptide mass fingerprinting analysis identified the large form of galanin-LI as progalanin without its signal sequence. In addition, galanin-LI was located in the Golgi bodies and vesicle-like structures of the fibroblasts. Furthermore, the addition of brefeldin A, an inhibitor of transport from the ER, decreased the release of galanin-LI. In this study, we showed that the fibroblast, a nonneural and nonendocrine cell type, produced and released a galanin precursor, progalanin, without processing via Golgi bodies or secretory vesicles.
{"title":"Expression and release of progalanin in fibroblasts","authors":"Hiroyuki Yamamoto , Kazuaki Iguchi , Keiko Unno , Kazuhiko Kaji , Minoru Hoshino","doi":"10.1016/j.regpep.2014.09.004","DOIUrl":"10.1016/j.regpep.2014.09.004","url":null,"abstract":"<div><p><span><span><span>Galanin<span> is a neuropeptide expressed in the central and peripheral nervous systems. Galanin is known to be biosynthesized in neural and </span></span>endocrine cells, but little evidence exists for its synthesis in other cells. In this study, we explored galanin-releasing nonneural cells using </span>radioimmunoassay<span>, finding that some fibroblasts produced and released the galanin-like immunoreactive component (galanin-LI). The molecular weight of the galanin-LI obtained from the fibroblasts, as measured by gel filtration chromatography<span> and Western blotting, was 14</span></span></span> <span><span><span><span>kDa and suggested that the compound was progalanin. Peptide mass fingerprinting analysis identified the large form of galanin-LI as progalanin without its </span>signal sequence. In addition, galanin-LI was located in the Golgi bodies and vesicle-like structures of the fibroblasts. Furthermore, the addition of </span>brefeldin A<span>, an inhibitor of transport from the ER, decreased the release of galanin-LI. In this study, we showed that the fibroblast, a nonneural and nonendocrine cell type, produced and released a galanin precursor, progalanin, without processing via Golgi bodies or </span></span>secretory vesicles.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"194 ","pages":"Pages 55-62"},"PeriodicalIF":0.0,"publicationDate":"2014-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.09.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32675111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.07.004
G. Telegdy , A. Adamik
Neuromedin U (NmU), first was isolated from the porcine spinal cord, has subsequently been demonstrated in a number of species, in which it is present in the periphery and also the brain. Two receptors have been identified: NmU1R is mainly present in peripheral tissues, and Nmu2R in the central nervous system. NmU, a potent endogenous anorectic, serves as a catabolic signaling molecule in the brain; it inhibits food uptake, increases locomotion, activates stress mechanism, having cardiovasscular effects and, causes hyperthermia. The mechanism of this hyperthermia is unknown. In the present experiments, the effects of NmU on the colon temperature following i.c.v administration were studied in rats. For an investigation of the possible role of receptors in mediating hyperthermia, the animals were treated simultaneously with CRF 9–41 and antalarmin, a CRH1 receptor inhibitors, astressin 2B, a CRH2 receptor antagonist, haloperidol a dopamine receptor antagonist, atropine a muscarinic cholinergic receptor antagonist, noraminophenazone a cyclooxygenase inhibitor or isatin, a prostaglandin receptor antagonist.
NmU increased the colon temperature, maximal action being observed at 2–3 h. CRF 9–41, antalarmin, astressin 2B haloperidol, atropine, noraminophenazone and isatin prevented the NmU-induced increase in colon temperature.
The results demonstrated that, when injected into the lateral brain ventricle NmU increased the body temperature, mediated by CRHR1 and CRHR2, dopamine and muscarinic cholinergic receptors. The final pathway involves prostaglandin.
{"title":"Mediators involved in the hyperthermic action of neuromedin U in rats","authors":"G. Telegdy , A. Adamik","doi":"10.1016/j.regpep.2014.07.004","DOIUrl":"10.1016/j.regpep.2014.07.004","url":null,"abstract":"<div><p><span><span>Neuromedin U (NmU), first was isolated from the porcine spinal cord, has subsequently been demonstrated in a number of species, in which it is present in the periphery and also the brain. Two receptors have been identified: NmU1R is mainly present in peripheral tissues, and Nmu2R in the </span>central nervous system<span>. NmU, a potent endogenous anorectic, serves as a catabolic signaling molecule in the brain; it inhibits food uptake, increases locomotion, activates stress mechanism, having cardiovasscular effects and, causes hyperthermia. The mechanism of this hyperthermia is unknown. In the present experiments, the effects of NmU on the colon temperature following i.c.v administration were studied in rats. For an investigation of the possible role of receptors in mediating hyperthermia, the animals were treated simultaneously with CRF 9–41 and </span></span>antalarmin<span>, a CRH1 receptor inhibitors, astressin 2B, a CRH2 receptor antagonist<span>, haloperidol<span><span> a dopamine receptor antagonist, atropine a muscarinic cholinergic receptor antagonist, noraminophenazone a cyclooxygenase inhibitor or </span>isatin<span>, a prostaglandin receptor antagonist.</span></span></span></span></p><p>NmU increased the colon temperature, maximal action being observed at 2–3<!--> <!-->h. CRF 9–41, antalarmin, astressin 2B haloperidol, atropine, noraminophenazone and isatin prevented the NmU-induced increase in colon temperature.</p><p><span>The results demonstrated that, when injected into the lateral brain ventricle NmU increased the body temperature, mediated by CRHR1 and CRHR2, dopamine and </span>muscarinic cholinergic receptors. The final pathway involves prostaglandin.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 24-29"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.07.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32572264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.06.001
Amândio Rocha-Sousa
{"title":"The ghrelin–GHSR-1a system in the ocular neuro-humoral regulation. Pearls and controversies","authors":"Amândio Rocha-Sousa","doi":"10.1016/j.regpep.2014.06.001","DOIUrl":"10.1016/j.regpep.2014.06.001","url":null,"abstract":"","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 53-54"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.06.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32426948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.08.004
Takeshi Soeki
{"title":"Ghrelin and its receptor: The role of the ghrelin signaling system in regulating cardiac function","authors":"Takeshi Soeki","doi":"10.1016/j.regpep.2014.08.004","DOIUrl":"10.1016/j.regpep.2014.08.004","url":null,"abstract":"","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 57-58"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.08.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32629762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.07.003
Song Guo , Filippa Barringer , Nora E. Zois , Jens P. Goetze , Messoud Ashina
Natriuretic peptides have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response on cerebral vessels.
{"title":"Natriuretic peptides and cerebral hemodynamics","authors":"Song Guo , Filippa Barringer , Nora E. Zois , Jens P. Goetze , Messoud Ashina","doi":"10.1016/j.regpep.2014.07.003","DOIUrl":"10.1016/j.regpep.2014.07.003","url":null,"abstract":"<div><p>Natriuretic peptides<span> have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment in decompensated disease. In contrast, their biological effects on the cerebral hemodynamics<span> are poorly understood. In this mini-review, we summarize the hemodynamic effects of the natriuretic peptides with a focus on the cerebral hemodynamics. In addition, we will discuss its potential implications in diseases where alteration of the cerebral hemodynamics plays a role such as migraine and acute brain injury including stroke. We conclude that a possible role of the peptides is feasible as evaluated from animal and in vitro studies, but more research is needed in humans to determine the precise response on cerebral vessels.</span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 15-23"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.07.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32571750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.08.003
Luis E. Flores , Héctor Del Zotto , Florencia Fragapane , Bárbara Maiztegui , Carolina L. Román , Antonio C. Boschero , Juan J. Gagliardino
Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.
{"title":"Islet neogenesis-associated protein (INGAP): The role of its endogenous production as a positive modulator of insulin secretion","authors":"Luis E. Flores , Héctor Del Zotto , Florencia Fragapane , Bárbara Maiztegui , Carolina L. Román , Antonio C. Boschero , Juan J. Gagliardino","doi":"10.1016/j.regpep.2014.08.003","DOIUrl":"10.1016/j.regpep.2014.08.003","url":null,"abstract":"<div><p>Islet neogenesis-associated protein (INGAP) is a peptide found in pancreatic exocrine-, duct- and islet- non-β-cells from normal hamsters. Its increase induced by either its exogenous administration or by the overexpression of its gene enhances β-cell secretory function and increases β-cell mass by a combination of stimulation of cell replication and islet neogenesis and reduction of β-cell apoptosis. We studied the potential modulatory role of endogenous INGAP in insulin secretion<span> using two different experimental approaches. Hamster islets transfected with INGAP-small interfering RNA (INGAP-siRNA) were used to study glucose-stimulated insulin secretion (GSIS). In parallel, freshly isolated islets were incubated with high glucose and the same concentration of either a specific anti-INGAP rabbit serum or normal rabbit serum. INGAP-siRNA transfected islets reduced their INGAP mRNA and protein content by 35.1% and 47.2%, respectively whereas GSIS decreased by 25.8%. GSIS by transfected islets attained levels comparable to those recorded in control islets when INGAP pentadecapeptide (INGAP-PP) was added to the culture medium. INGAP antibody in the medium decreased significantly GSIS in a dose-dependent manner. These results indicate that endogenous INGAP plays a “physiological” positive modulatory role in insulin secretion, supporting its possible use in the treatment of prediabetes and Type 2 diabetes.</span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 30-34"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.08.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32617014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.08.005
Yao Shen, Yueyang Tian, Jianbo Yang, Xiaojie Shi, Li Ouyang, Jieqiong Gao, Jianxin Lu
Objective
The aim of this study was to investigate the effects of carnosine on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions.
Methods
The Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions.
Results
Under the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72 ± 1.59 pmol/min/μg protein and 3.95 ± 0.28 mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~ 42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8 h of oxygen–glucose deprivation (OGD) followed by 24 h of recovery under the normal growth condition.
Conclusions
Carnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury.
{"title":"Dual effects of carnosine on energy metabolism of cultured cortical astrocytes under normal and ischemic conditions","authors":"Yao Shen, Yueyang Tian, Jianbo Yang, Xiaojie Shi, Li Ouyang, Jieqiong Gao, Jianxin Lu","doi":"10.1016/j.regpep.2014.08.005","DOIUrl":"10.1016/j.regpep.2014.08.005","url":null,"abstract":"<div><h3>Objective</h3><p>The aim of this study was to investigate the effects of carnosine<span> on the bioenergetic profile of cultured cortical astrocytes under normal and ischemic conditions.</span></p></div><div><h3>Methods</h3><p>The Seahorse Bioscience XF96 Extracellular Flux Analyzer was used to measure the oxygen consumption rates (OCRs) and extracellular acidification rates (ECARs) of cultured cortical astrocytes treated with and without carnosine under normal and ischemic conditions.</p></div><div><h3>Results</h3><p><span>Under the normal growth condition, the basal OCRs and ECARs of astrocytes were 21.72</span> <!-->±<!--> <!-->1.59<!--> <!-->pmol/min/μg protein and 3.95<!--> <!-->±<!--> <!-->0.28<!--> <span>mpH/min/μg protein respectively. Mitochondrial respiration accounted for ~</span> <span>80% of the total cellular respiration and 85% of this coupled to ATP synthesis. Carnosine significantly reduced basal OCRs and ECARs and ATP-linked respiration, but it strikingly increased the spare respiratory capacity of astrocytes. The cellular ATP level in carnosine-treated astrocytes was reduced to ~</span> <!-->42% of the control. However, under the ischemic condition, carnosine upregulated the mitochondrial respiratory and cellular ATP content of astrocytes exposed to 8<!--> <!-->h of oxygen–glucose deprivation (OGD) followed by 24<!--> <!-->h of recovery under the normal growth condition.</p></div><div><h3>Conclusions</h3><p>Carnosine may be an endogenous regulator of astrocyte energy metabolism and a clinically safe therapeutic agent for promoting brain energy metabolism recovery after ischemia/reperfusion injury.</p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 45-52"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.08.005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32646415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-06-01DOI: 10.1016/j.regpep.2014.08.002
Chun-Mei Zhao , Yosuke Kodama , Arnar Flatberg , Vidar Beisvag , Bård Kulseng , Arne K. Sandvik , Jens F. Rehfeld , Duan Chen
The stomach produces acid, which may play an important role in the regulation of bone homeostasis. The aim of this study was to reveal signaling pathways in the gastric mucosa that involve the acid secretion and possibly the bone metabolism in CCK1 and/or CCK2 receptor knockout (KO) mice. Gastric acid secretion was impaired and the ECL cell signaling pathway was inhibited in CCK2 receptor KO mice but not in CCK1 receptor KO mice. However, in CCK1 + 2 receptor double KO mice the acid secretion in response to pylorus ligation-induced vagal stimulation and the ECL cell pathway were partially normalized, which was associated with an up-regulated pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1). The basal part of the gastric mucosa expressed parathyroid hormone-like hormone (PTHLH) in a subpopulation of likely ECL cells (and possibly other cells) and vitamin D3 1α hydroxylase probably in trefoil peptide2-immunoreactive cells. In conclusion, mice lacking CCK receptors exhibited a functional shift from the gastrin-CCK pathways to the neuronal pathway in control of the ECL cells and eventually the acid secretion. Taking the present data together with previous findings, we suggest a possible link between gastric PTHLH and vitamin D and bone metabolism.
{"title":"Gene expression profiling of gastric mucosa in mice lacking CCK and gastrin receptors","authors":"Chun-Mei Zhao , Yosuke Kodama , Arnar Flatberg , Vidar Beisvag , Bård Kulseng , Arne K. Sandvik , Jens F. Rehfeld , Duan Chen","doi":"10.1016/j.regpep.2014.08.002","DOIUrl":"10.1016/j.regpep.2014.08.002","url":null,"abstract":"<div><p><span><span>The stomach produces acid, which may play an important role in the regulation of bone homeostasis<span>. The aim of this study was to reveal signaling pathways<span> in the gastric mucosa that involve the </span></span></span>acid secretion and possibly the bone metabolism in CCK</span><sub>1</sub> and/or CCK<sub>2</sub><span> receptor knockout (KO) mice. Gastric acid secretion<span> was impaired and the ECL cell signaling pathway was inhibited in CCK</span></span><sub>2</sub> receptor KO mice but not in CCK<sub>1</sub> receptor KO mice. However, in CCK<sub>1<!--> <!-->+<!--> <!-->2</sub><span> receptor double KO mice the acid secretion in response to pylorus ligation-induced vagal stimulation and the ECL cell pathway were partially normalized, which was associated with an up-regulated pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1). The basal part of the gastric mucosa expressed parathyroid hormone-like hormone (PTHLH) in a subpopulation of likely ECL cells (and possibly other cells) and vitamin D3<span> 1α hydroxylase<span><span> probably in trefoil peptide2-immunoreactive cells. In conclusion, mice lacking CCK receptors exhibited a functional shift from the gastrin-CCK pathways to the neuronal pathway in control of the ECL cells and eventually the acid secretion. Taking the present data together with previous findings, we suggest a possible link between gastric PTHLH and </span>vitamin D and bone metabolism.</span></span></span></p></div>","PeriodicalId":20853,"journal":{"name":"Regulatory Peptides","volume":"192 ","pages":"Pages 35-44"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.regpep.2014.08.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32617585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}