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Journal Article

Quantitative distribution and localization of calcitonin gene-related peptide-like cells in the stomach of two kidney, one clip rats.

01 Jun 2009-Journal of Physiology and Pharmacology (J Physiol Pharmacol)-Vol. 60, Iss: 2, pp 35-39

TL;DR: The aim of the present study was to examine the number and distribution of CGRP-containing cells in the pylorus of "two kidney, one clip" (2K1C) renovascular hypertension model in rats and the changes induced by hypertension in the neuroendocrine cells containing C GRP of the rats.

AbstractThe majority of research for the calcitonin gene-related peptide (CGRP) in the stomach in the hypertension has been devoted to the submucosal blood flow, and no attention has been paid to its quantitative distribution in the gastric neuroendocrine cells. The aim of the present study was to examine the number and distribution of CGRP-containing cells in the pylorus of "two kidney, one clip" (2K1C) renovascular hypertension model in rats. The studies were carried out on the stomach of rats. After 6 week period of the renal artery clipping procedure, eight 2K1C rats developed stable hypertension. The hypertension significantly increased the number of endocrine cells pylorus immunoreactive to calcitonin gene-related peptide (CGRP) antisera. The differences between the hypertensive rats and the control group concerned not only the number of endocrine cells but also their distribution. CGRP participates in the regulation of cardiovascular functions both in normal state and in the pathophysiology of hypertension through interactions with the prohypertensive systems. The changes induced by hypertension in the neuroendocrine cells containing CGRP of the rats are discussed.

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Journal ArticleDOI
TL;DR: This study aims to identify, localize, and assess changes in CART-immunopositive structures of the gastrointestinal tract (GI tract) of rats with renovascular hypertension, and detects CART in the extensive population of neurons and in neuroendocrine cells.
Abstract: The prevalence of CART (cocaine- and amphetamine-regulated transcript) throughout the organism, multiplicity of functions fulfilled by that peptide, and the collected evidence confirming CART contribution to blood pressure regulation prompted us to undertake the research aiming to identify, localize, and assess changes in CART-immunopositive structures of the gastrointestinal tract (GI tract) of rats with renovascular hypertension. The two-kidney one-clip model of arterial hypertension was used to evaluate the location and density of CART-containing structures in the stomach (cardia, fundus, and pylorus), duodenum, jejunum, ileum, and colon of hypertensive rats. The study was carried out on the GI tract of 20 rats. Ten rats were subjected to the renal artery clipping procedure and after a 6-week period each of them developed stable hypertension. An immunohistochemical localization of CART was performed on paraffin GI tract sections from all the study animals. CART was detected in the extensive population of neurons, particularly within the myenteric plexuses all along the GI tract, and also in neuroendocrine cells, being especially numerous in the stomach and a few in the small intestine. The hypertension significantly increased the density of CART-positive structures in the rat GI tract. The differences between the hypertensive rats and the control animals concerned not only the density of CART-immunoreactive structures but also the staining intensity. As this study provides novel findings, we are planning further molecular examinations to better understand the impact of hypertension on the functioning and activity of CART in the GI tract. © 2012 International Union of Biochemistry and Molecular Biology, Inc.

18 citations


Cites background or result from "Quantitative distribution and local..."

  • ...Considering that in previous research we proved likewise greater number of CGRP-IR endocrine cells in the stomach of 2K1C rats when compared with the control group, we might suggest the impaired protective and secretory mechanisms in the hypertensive rats [16]....

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  • ...There is some clinical and experimental evidence for the involvement of neuropeptides and proinflammatory markers in the pathogenesis of arterial hypertension [16,34,36]....

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  • ...The experimental data, and also numerous clinical observations, indicate a significant role of humoral factors and neurotransmitters in the pathogenesis of arterial hypertension [9,16]....

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  • ...As there is evidence [16,17] confirming the influence of hypertension on the activity of CGRP-containing cells, considerable changes may be expected in the content of CART peptide in animals with renovascular hypertension....

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Journal ArticleDOI
TL;DR: It has been shown that acrylamide induces a significant response of ENS neurons even in TDI dose, which suggests that it is not neutral to the body.
Abstract: Acrylamide is one of the food toxins to which the human body is exposed. Although researchers’ interest in acrylamide has been growing in recent years, the knowledge of its effect on the gastrointestinal tract, especially on intramural neurons which form the enteric nervous system is scarce. The aim of this experiment was to determine the influence of acrylamide, administered at doses equivalent to the human tolerable daily intake (TDI, 0.5 μg/kg b.w./day) and ten times higher than the TDI (5 μg/kg b.w./day), on the distribution of vasoactive intestinal peptide (VIP), substance P (SP), and calcitonin gene related peptide (CGRP) in intramural neurons of the domestic pig stomach. Using double immunofluorescent labelling we revealed that the ENS neurons underwent adaptive changes in response to the supplementation of acrylamide, which manifested themselves as increased expression of VIP, SP and CGRP, both in intramural neurons and by an increase in the nerve density in submucous and muscular layers in the porcine stomach. These substances take part in defensive reactions of neurons and transmission of sensory reactions may play an important role in protecting the stomach against the harmful effect of acrylamide. Moreover, it has been shown that acrylamide induces a significant response of ENS neurons even in TDI dose, which suggests that it is not neutral to the body. These findings may be the basis for further toxicological studies addressing the question if currently permitted minimal content of acrylamide in the food does jeopardize the health of human consumers?

14 citations


Cites background or result from "Quantitative distribution and local..."

  • ...In addition, calcitonin gene related peptide (CGRP) was originally identified as a product of alternative processing of RNA of the calcitonin gene in the rat brain and is common in neurons and nerves in the gastrointestinal tract as well as in the central and peripheral nervous system (Hayakawa et al., 2009; Kasacka, 2009; Lee and Nam, 2006; Timmermans et al., 1992; Toole et al., 1998)....

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  • ...…of alternative processing of RNA of the calcitonin gene in the rat brain and is common in neurons and nerves in the gastrointestinal tract as well as in the central and peripheral nervous system (Hayakawa et al., 2009; Kasacka, 2009; Lee and Nam, 2006; Timmermans et al., 1992; Toole et al., 1998)....

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  • ...These findings are similar to those of earlier studies on rodents, mammals and humans (Kaleczyc et al., 2007; Kasacka, 2009; Pimont et al., 2003; Schemann et al., 2001)....

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Journal ArticleDOI
TL;DR: Investigations demonstrated the impact of renovascular hypertension on the neuroendocrine system in the rat stomach and changes in the total number and ultrastructure of DNES cells proved their undeniable role in the modulation of gastric dysfunction, as a consequence of deregulation of homeostasis-maintaining systems.
Abstract: Purpose The aim of the present study was to perform immunohistochemical and ultrastructural analysis of gastrin-, synaptophysin (SY)- and atrial natriuretic peptide (ANP)-positive cells in the pylorus of “two kidney, one clip” (2K1C) renovascular hypertension model in rats. Material/methods In order to identify neuroendocrine (NE) cells, immunohistochemical reactions were performed with the use of specific antibodies against gastrin, SY and ANP. Gastric NE cells were also examined using an electron microscope. Results The present study revealed a twofold increase in the number of gastrin- and SY-positive cells and a significant decrease in the number of ANP-immunoreactive (IR) cells in the pyloric mucosa of 2K1C rats. Test results obtained with an electron microscope confirmed a change in the activity of the stomach endocrine cells of hypertensive rats. Conclusions Immunohistochemical and ultrastructural investigations demonstrated the impact of renovascular hypertension on the neuroendocrine system in the rat stomach. The changes in the total number and ultrastructure of DNES cells proved their undeniable role in the modulation of gastric dysfunction, as a consequence of deregulation of homeostasis-maintaining systems.

6 citations


Cites background from "Quantitative distribution and local..."

  • ...activity of parietal cells and blood flow through the gastric mucosa [1,2,27]....

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  • ...Many investigations have indicated that in various pathological ates the number and morphology of NE cells in the stomach dergo some changes [1,2,12]....

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  • ...Several experimental studies have demonstrated that hypertension causes disturbances in the secretion of neuropeptides and biogenic amines in the majority of organs, including the digestive system [1,2]....

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  • ...This seems to confirm the volvement of biologically active substances produced by stroendocrine cells in various pathological and adaptive ocesses in the body [1,2,12]....

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Journal ArticleDOI
TL;DR: It was revealed that renovascular hypertension caused changes in the neuroendocrine, CGRP-containing cells in the lungs of rats in the two-kidney, one-clip (2K1C) renov vascular hypertension model.
Abstract: Taking into consideration renal hypertension-induced homeostatic disorders and the key role of calcitonin gene-related peptide (CGRP)Â in many, systemic functions regulating systems, a question arises as to what an extent arterial hypertension affects the morphology and dynamics of pulmonary CGRP-immunopositive cell changes. The aim of the present study was to examine the distribution, morphology and dynamics of changes of CGRP-containing cells in the lungs of rats in the two-kidney, one-clip (2K1C) renovascular hypertension model. The studies were carried out on the lungs of rats after 3, 14, 28, 42, and 91 days long period from the renal artery clipping procedure. In order to identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against CGRP. It was revealed that renovascular hypertension caused changes in the neuroendocrine, CGRP-containing cells in the lungs of rats. The changes, observed in the neuroendocrine cells, depended on time periods from experimentally induced hypertension. The highest intensity of changes in the neuroendocrine cells was observed in the lungs of rats after 14 days from the surgery.

6 citations


Journal ArticleDOI
TL;DR: Results obtained in many research studies indicate intense activity of enteroendocrine cells in the gastrointestinal tract in various pathological conditions, including hypertension.
Abstract: ____________________________________________________________________________________________________ Recent years have witnessed a progressive increase in the number of people suffering from hypertension, which is one of the most serious health problems in the world. Hypertension results in changes leading to function disorders, not only of the organs and tissues, but also changes leading to the activation of many defense mechanisms in the cells in order to prevent damage. One of them is the expression of neuroendocrine (NE) hormones and biologically active substances, which has been the focus of extensive research for a number of years. Active involvement of NE cells and the biological and therapeutic properties of various substances synthesized by them have been confirmed in clinical trials and in various experimental models. Results obtained in many research studies indicate intense activity of enteroendocrine cells in the gastrointestinal tract in various pathological conditions, including hypertension. In the present review, we discuss the morphological and functional changes of gastrointestinal neuroendocrine cells under conditions of different types of hypertension.

3 citations


Cites background from "Quantitative distribution and local..."

  • ...This illustrates the important role played by these cells in maintaining whole body homeostasis [45,46,47]....

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References
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Journal ArticleDOI
TL;DR: This work has shown that alternative tissue-specific processing of primary mRNA from the α-CT/CGRP gene in rats generates two distinct peptides, CT and CGRP, which are the most potent endogenous vasodilatory peptides that have been discovered.
Abstract: I. Introduction THE calcitonin (CT) and calcitonin gene-related peptide (CGRP) are derived from the CT/CGRP gene, which is localized in chromosome 11. Alternative splicing of the primary RNA transcript leads to the translation of CGRP and CT peptides in a tissue-specific manner. This alternative tissue-specific processing of primary mRNA from the α-CT/CGRP gene in rats generates two distinct peptides, CT and CGRP (1, 2). CGRP is a 37-amino acid neuropeptide expressed predominantly in the nervous system and CT is expressed mainly in the thyroid gland. CGRP receptors, widely distributed in the body, are the most potent endogenous vasodilatory peptides that have been discovered. Derived from the C cells of the thyroid gland, CT is the most potent peptide inhibitor of osteoclast-mediated bone resorption and is involved primarily in protecting the skeleton during periods of “calcium stress” such as growth, pregnancy, and lactation (3). In 1961, Copp and colleagues (4) postulated the existence of the calcium-lo...

477 citations


"Quantitative distribution and local..." refers background in this paper

  • ...The reported levels of circulating immunoreactive CGRP in hypertensive humans have been conflicting (32)....

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Journal ArticleDOI
TL;DR: The new biology suggests that gastrointestinal hormones should be conceived as intercellular messengers of general physiological impact rather than as local regulators of the upper digestive tract.
Abstract: Rehfeld, Jens F. The New Biology of Gastrointestinal Hormones. Physiol. Rev. 78: 1087–1108, 1998. — The classic concept of gastrointestinal endocrinology is that of a few peptides released to the c...

303 citations


Additional excerpts

  • ...involvement of neuropeptides in the pathogenesis (8-11)....

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Journal ArticleDOI
Alan R. Giles1

273 citations


"Quantitative distribution and local..." refers methods in this paper

  • ...Procedures involving the animals and their care were conducted in conformity with the institutional guidelines that are in compliance with national and international law and with guidelines for the use of animals in biomedical research (22)....

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Journal Article
TL;DR: Gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents, unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia.
Abstract: Since Robert discovery that pretreatment with prostaglandin (PG) applied in non-antisecretory dose can prevent the injury of gastric mucosa induced by necrotizing agents, much attention was paid to the role of these cyclooxygenase (COX) products in the mechanism of gastric mucosal integrity and ulcer healing. The ability of exogenous PG to attenuate or even completely prevent mucosal damage caused by corrosive substances such as absolute ethanol, hyperosmolar solutions or concentrated bile has been termed "cytoprotection". Increased generation of endogenous PG in the gastric mucosa exposed to the topical contact with "mild irritant" such as 20% ethanol, 1 mM NaCl or 5 mM taurocholate also prevented gastric injury caused by strong irritants via phenomenon of adaptive cytoprotection. Other mediators such as growth factors, nitric oxide (NO) or calcitonin gene related peptide (CGRP) as well as some gut hormones including gastrin and cholecystokinin (CCK), leptin, ghrelin and gastrin-releasing peptide (GRP) have been also found to protect gastric mucosa against the damage induced by corrosive substances. This protective action of gut hormones has been attributed to the release of PG or activation of sensory nerves because it could be abolished by the pretreatment with indomethacin or large neurotoxic dose of capsaicin and restored by the addition of exogenous PGE(2) or CGRP, respectively. Short (5 min) ischemia of the stomach applied before prolonged ischemia-reperfusion (I/R) attenuated markedly the gastric lesions produced by this I/R and also prevented the mucosal damage provoked by necrotizing substances. This protection could be abolished by the pretreatment with non-steroidal anti-inflammatory drugs (NSAID) and was accompanied by an enhancement of gastric mucosal COX-2 expression and activity. Exposure of gastric mucosa to single insult of acidified aspirin (ASA) causes severe mucosal damage with occurrence of multiple haemorrhagic lesions but with repeated application of ASA, the attenuation of mucosal lesions is observed, despite the profound inhibition of PGE(2) generation. This phenomenon called "gastric adaptation" does not appear to depend upon endogenous biosynthesis of PG but possibly involves enhanced production of growth factors increasing cell proliferation and mucosal regeneration. Unlike short lived gastroprotection by PG, NO, CGRP, mild irritants or short ischemia, gastric adaptation appears to be long-lasting phenomenon accompanied by increased resistance of the adapted mucosa to subsequent damage induced by corrosive agents.

183 citations


"Quantitative distribution and local..." refers background or methods in this paper

  • ...Immunopositive cells were counted in five (5) randomly selected microscopic fields, each field of 0....

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  • ...diverse hormones, neurotransmitters, cytokines and growth factors (5)....

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  • ...Peptide hormones, cytokines, chemocines, integrins, other related molecules regulate homeostasis in the tissue of external systems that facilitate restoration of local homeostasis (5, 6)....

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Journal Article
TL;DR: It is concluded that MS features of obesity are closely related to fasting and postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin, suggesting that determination of gut hormones controlling food intake might be considered as a valuable tool to assess the progression of MS to comorbidities of obesity.
Abstract: Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin resistance, hypertension, dyslipidemia and glucose intolerance, has been associated with inflammatory biomarkers and cardiovascular diseases. This study was carried out on three groups of women; lean controls, moderately obese with MS (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3-36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions and in response to a standard mixed meal, and 2. to elucidate the relationship between the plasma levels of these gut peptides and metabolic syndrome parameters. Plasma levels of the gut hormones were measured by radioimmunoassays at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion. Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the strongest biomarker of inflammation were also determined in OB-MS and MOB-MS. When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters such as waist circumference, higher fat mass and higher plasma levels of low density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups revealed significantly higher values of body mass index (BMI), fat mass, total cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and acylated ghrelin levels were significantly lower in OB-MS compared to lean women. In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than in lean women. The fasting plasma levels of total and acylated ghrelin and their postprandial decrease were significantly smaller in both obese groups compared to lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin, whilst it negatively correlated with plasma fasting and total ghrelin. Moreover, plasma fasting acylated ghrelin correlated positively with fat mass. Fasting total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR. We conclude that MS features of obesity are closely related to fasting and postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin, suggesting that determination of gut hormones controlling food intake might be considered as a valuable tool to assess the progression of MS to comorbidities of obesity.

159 citations


"Quantitative distribution and local..." refers background in this paper

  • ...After this time, eight (8) 2K1C rats developed stable hypertension....

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  • ...involvement of neuropeptides in the pathogenesis (8-11)....

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