β-Casomorphin-7 regulates the secretion and expression of gastrointestinal mucins through a μ-opioid pathway

2006 ◽  
Vol 290 (6) ◽  
pp. G1105-G1113 ◽  
Author(s):  
Sandra Zoghbi ◽  
Aurélien Trompette ◽  
Jean Claustre ◽  
Mahmoud El Homsi ◽  
Javier Garzón ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Goblet Cells ◽  
Receptor Activation ◽  
Opioid Antagonist ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Mucin Secretion ◽  
Protective Function ◽  
Mucin Production ◽  
Μ Opioid Receptors

We have recently shown that β-casomorphin-7, a milk opioid peptide, strongly stimulates mucin secretion in the rat jejunum through a nervous pathway and opioid receptor activation. In this study, the hypothesis that β-casomorphin-7 may also act directly on intestinal goblet cells was investigated in vitro in rat and human intestinal mucin-producing cells (DHE and HT29-MTX) using quantitative and semiquantitative RT-PCR and ELISA. The presence of μ-opioid receptors was demonstrated in rat goblet cells in the upper half of the colonic crypt and in the two cell lines by immunohistochemistry and RT-PCR. In rat DHE cells, β-casomorphin-7 increased the expression of rat mucin (rMuc)2 and rMuc3 but not rMuc1, rMuc4, and rMuc5AC. This effect was time and dose dependent, with the maximum of increase in transcripts being noticed for a concentration of 10−4 M after 2 h of stimulation for rMuc2 (225% of controls) and 4 h of stimulation for rMuc3 (208% of controls). Mucin secretion was maximally increased after 8 h of stimulation. Interestingly, these effects were prevented by pretreatment of the cells with the μ-opioid antagonist cyprodime. In human HT29-MTX cells, β-casomorphin-7 (10−4 M) also increased MUC5AC mRNA levels (219% after 24 h of stimulation) and the secretion of this mucin (169% of controls). In conclusion, β-casomorphin-7 may contribute significantly to mucin production via a direct effect on intestinal goblet cells and the activation of μ-opioid receptors. Because intestinal mucins have a crucial mucosal protective function, dairy products containing β-casomorphin-7 may improve intestinal protection and could have dietary and health applications.

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

2005 ◽  
Vol 288 (3) ◽  
pp. R723-R732 ◽  
Author(s):  
Wei-Hua Cao ◽  
Shaun F. Morrison
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Opioid Receptors ◽  
Receptor Activation ◽  
Opioid Antagonist ◽  
Ventrolateral Medulla ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Raphe Pallidus ◽  
Μ Opioid Receptors

μ-Opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 μg/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 μg (10 nmol) in 10 μl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8°C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 μl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central μ-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central μ-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.

scholarly journals Subchronic exposure to acrylamide affects colon mucin secretion in juvenile wistar rats

2016 ◽  
Vol 68 (3) ◽  
pp. 641-649 ◽  
Author(s):  
Ivana Koledin ◽  
Renata Kovac ◽  
Vesna Rajkovic ◽  
Milica Matavulj
Keyword(s):  
Adverse Effect ◽  
Goblet Cell ◽  
Wistar Rats ◽  
Goblet Cells ◽  
Mucin Secretion ◽  
Human Diet ◽  
Mucin Production ◽  
High Carbohydrate ◽  
Antibody Staining ◽  
Male Wistar Rats

Acrylamide (AA) is an important industrial chemical worldwide. AA also forms naturally in many high-carbohydrate foods (bread, French fries, coffee, etc.) when they are heated. Since AA is ubiquitous in the human diet, and more than one-third of the calories we take in each day come from foods with detectable levels of acrylamide, the aim of this study was to determine the effect of subchronic AA treatment on colon goblet cell mucin secretion. Male Wistar rats were gavaged with AA for 5 days a week for 21 days. The animals were divided into three groups that were gavaged with different AA concentrations (0, 25, 50 mg/kg/day). Colon samples were processed for histochemical (PAS-AB, HID-AB) and immunohistochemical (anti-rat MUC2 antibody) staining to visualize mucins in the goblet cells. AA treatment showed an alteration in mucin production and secretion in that the amount of all investigated mucin types dropped. More prominent changes were detected in the upper crypt part where a decreased number of goblet cell was observed. AA treatment elicited a significant reduction in neutral mucins, while acidic mucins showed linearly decreasing trend with respect to AA doses. Also, a linear reduction of MUC2 mucins was noticed. Sulfomucins were absent in the colon lower crypt in all experimental groups, while in the upper crypt both sulfo- and sialomucins were significantly decreased. The results of our study point to changes in the synthesis, differentiation and distribution of mucins after AA treatment, which can have adverse effect on colorectal health.

Mucin secretion and PKC isoforms in SPOC1 goblet cells: differential activation by purinergic agonist and PMA

2003 ◽  
Vol 285 (1) ◽  
pp. L149-L160 ◽  
Author(s):  
Lubna H. Abdullah ◽  
Jason T. Bundy ◽  
Camille Ehre ◽  
C. William Davis
Keyword(s):  
Goblet Cells ◽  
Independent Effect ◽  
Rt Pcr ◽  
Mucin Secretion ◽  
Binding Partner ◽  
Pkc Isoforms ◽  
C1 Domain ◽  
Phorbol Ester Receptor ◽  
Enzyme Mapping ◽  
First Time

SPOC1 cells, which are a mucin-secreting model of rat airway goblet cells, possess a luminal P2Y2 purinoceptor through which UTP, ATP, and ATPγS stimulate secretion with EC50 values of ∼3 μM. PMA elicits mucin secretion with high EC50 (75 nM) and saturation (300 nM) values. For the first time in airway mucin-secreting cells, the PKC isoforms expressed and activated by a secretagogue were determined using RT-PCR/restriction-enzyme mapping and Western blotting. Five isoforms were expressed: cPKCα, nPKCδ and -η, and aPKCζ and -ι/λ. PMA caused cPKCα and nPKCδ to translocate to the membrane fraction of SPOC1 cells; only nPKCδ so responded to ATPγS. Membrane-associated nPKCδ and mucin secretion increased in parallel with ATPγS concentration and yielded EC50 values of 2–3 μM and maximum values of 100 μM. Effects of PMA to increase membrane-associated cPKCα and nPKCδ saturated at 30 nM, whereas mucin secretion saturated at 300 nM, which suggests a significant PKC-independent effect of PMA on mucin secretion. A prime alternate phorbol ester-receptor candidate is the C1-domain protein MUNC13. RT-PCR revealed the expression of ubiquitous (ub)MUNC13-2 and its binding partner, DOC2-γ. Hence, P2Y2 agonists activate nPKCδ in SPOC1 cells. PMA activates cPKCα and nPKCδ at high affinity and stimulates a lower affinity PKC-independent pathway that leads to mucin secretion.

scholarly journals Altered Expression of Three EGFR Posttranslational Regulators MDGI, MIG6, and EIG121 in Invasive Breast Carcinomas

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Didier Meseure ◽  
Kinan Drak Alsibai ◽  
Sophie Vacher ◽  
Rana Hatem ◽  
Andre Nicolas ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Growth Inhibitor ◽  
Receptor Activation ◽  
Mrna Levels ◽  
Breast Carcinomas ◽  
Rt Pcr ◽  
Altered Expression ◽  
Invasive Breast Carcinomas

Epidermal growth factor receptor (EGFR) signalling is a highly regulated process with a tight balance between receptor activation and inactivation in invasive breast carcinomas (IBCs) particularly in triple-negative carcinomas (TNC). Clinical trials using anti-EGFR therapies are actually performed although no activating alterations (mutations, amplifications, or rearrangements) of EGFR have been clearly recognized in order to identify new targeted modalities for IBCs. We explored mammary-derived growth inhibitor (MDGI), estrogen-induced gene-121 (EIG121), and mitogen-induced gene-6 (MIG6), three posttranslational EGFR trafficking molecules implicated in EGFR spatiotemporal regulatory pathway. We quantified MDGI, EIG121, and MIG6 at mRNA levels by using real-time quantitative RT-PCR in a series of 440 IBCs and at protein levels by using immunohistochemistry in a series of 88 IBCs. Results obtained by RT-PCR showed that in IBCs, MDGI, MIG6, and EIG121 mRNA were mainly underexpressed (25.7%, 45.0%, and 16.1%, respectively) particularly in the TNC subtype for EIG121 (60.3%). We also observed mRNA overexpression of MDGI and EIG121, respectively, in 12.7% and 22.3% of IBCs. These altered mRNA expressions were confirmed at the protein level. Some links were found between expression patterns of these three genes and several classical pathological and clinical parameters. Only EIG121 was found to have a prognostic significance (p=0.0038). Altered expression of these three major EGFR posttranslational negative regulators could create an aberrant EGFR-mediated oncogenic signalling pathway in IBCs. MDGI, MIG6, and EIG121 expression status also may be potential useful biomarkers (sensitivity or resistance) in targeted EGFR therapy.

scholarly journals Co-incident signalling between μ-opioid and M3 muscarinic receptors at the level of Ca2+ release from intracellular stores: lack of evidence for Ins(1,4,5)P3 receptor sensitization

2003 ◽  
Vol 375 (3) ◽  
pp. 713-720 ◽  
Author(s):  
Damien S. K. SAMWAYS ◽  
Wen-hong LI ◽  
Stuart J. CONWAY ◽  
Andrew B. HOLMES ◽  
Martin D. BOOTMAN ◽  
...  
Keyword(s):  
Muscarinic Receptors ◽  
Opioid Receptors ◽  
Receptor Agonist ◽  
Flash Photolysis ◽  
Receptor Activation ◽  
Scanning Confocal Microscopy ◽  
Rate Of Decay ◽  
Μ Opioid Receptor ◽  
Μ Opioid Receptors ◽  
Insp3 Receptor

Activation of Gi/Go-coupled opioid receptors increases [Ca2+]i (intracellular free-Ca2+ concentration), but only if there is concomitant Gq-coupled receptor activation. This Gi/Go-coupled receptor-mediated [Ca2+]i increase does not appear to result from further production of InsP3 [Ins(1,4,5)P3] in SH-SY5Y cells. In the present study, fast-scanning confocal microscopy revealed that activation of μ-opioid receptors alone by 1 μM DAMGO ([d-Ala, NMe-Phe, Gly-ol]-enkephalin) did not stimulate the InsP3-dependent elementary Ca2+-signalling events (Ca2+ puffs), whereas DAMGO did evoke Ca2+ puffs when applied during concomitant activation of M3 muscarinic receptors with 1 μM carbachol. We next determined whether μ-opioid receptor activation might increase [Ca2+]i by sensitizing the InsP3 receptor to InsP3. DAMGO did not potentiate the amplitude of the [Ca2+]i increase evoked by flash photolysis of the caged InsP3 receptor agonist, caged 2,3-isopropylidene-InsP3, whereas the InsP3 receptor sensitizing agent, thimerosal (10 μM), did potentiate this response. DAMGO also did not prolong the rate of decay of the increase in [Ca2+]i evoked by flash photolysis of caged 2,3-isopropylidene-InsP3. Furthermore, DAMGO did not increase [Ca2+]i in the presence of the cell-membrane-permeable InsP3 receptor agonist, InsP3 hexakis(butyryloxymethyl) ester. Therefore it appears that μ-opioid receptors do not increase [Ca2+]i through either InsP3 receptor sensitization, enhancing the releasable pool of Ca2+ or inhibition of Ca2+ removal from the cytoplasm.

scholarly journals Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors

2012 ◽  
Vol 107 (3) ◽  
pp. 1022-1031 ◽  
Author(s):  
Melissa A. Herman ◽  
Richard A. Gillis ◽  
Stefano Vicini ◽  
Kenneth L. Dretchen ◽  
Niaz Sahibzada
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Receptor Activation ◽  
Membrane Excitability ◽  
Selective Blockade ◽  
Medial Nucleus ◽  
Opioid Receptor Agonist ◽  
Gaba Signaling ◽  
Μ Opioid Receptor ◽  
Μ Opioid Receptors

Our laboratory previously reported that gastric activity is controlled by a robust GABAA receptor-mediated inhibition in the medial nucleus of the tractus solitarius (mNTS) ( Herman et al. 2009 ), and that μ-opioid receptor activation inhibits gastric tone by suppression of this GABA signaling ( Herman et al. 2010 ). These data raised two questions: 1) whether any of this inhibition was due to tonic GABAA receptor-mediated conductance in the mNTS; and 2) whether μ-opioid receptor activation suppressed both tonic and phasic GABA signaling. In whole cell recordings from rat mNTS neurons, application of three GABAA receptor antagonists (gabazine, bicuculline, and picrotoxin) produced a persistent reduction in holding current and decrease in population variance or root mean square (RMS) noise, suggesting a blockade of tonic GABA signaling. Application of gabazine at a lower concentration abolished phasic currents, but had no effect on tonic currents or RMS noise. Application of the δ-subunit preferring agonist gaboxadol (THIP) produced a dose-dependent persistent increase in holding current and RMS noise. Pretreatment with tetrodotoxin prevented the action of gabazine, but had no effect on the THIP-induced current. Membrane excitability was unaffected by the selective blockade of phasic inhibition, but was increased by blockade of both phasic and tonic currents. In contrast, activation of tonic currents decreased membrane excitability. Application of the μ-opioid receptor agonist DAMGO produced a persistent reduction in holding current that was not observed following pretreatment with a GABAA receptor antagonist and was not evident in mice lacking the δ-subunit. These data suggest that mNTS neurons possess a robust tonic inhibition that is mediated by GABAA receptors containing the δ-subunit, that determines membrane excitability, and that is partially regulated by μ-opioid receptors.

scholarly journals Chronic treatment with the opioid antagonist naltrexone favours the coupling of spinal cord μ-opioid receptors to Gαz protein subunits

2012 ◽  
Vol 62 (2) ◽  
pp. 757-764 ◽  
Author(s):  
Elsa M. Valdizán ◽  
Alvaro Díaz ◽  
Fuencisla Pilar-Cuéllar ◽  
Aquilino Lantero ◽  
Ricardo Mostany ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Opioid Receptors ◽  
Chronic Treatment ◽  
Opioid Antagonist ◽  
Protein Subunits ◽  
Μ Opioid Receptors

scholarly journals Expression of glucose-dependent insulinotropic polypeptide in the zebrafish

2009 ◽  
Vol 297 (6) ◽  
pp. R1803-R1812 ◽  
Author(s):  
Michelle C. Musson ◽  
Lisa I. Jepeal ◽  
Patrick D. Mabray ◽  
Irina V. Zhdanova ◽  
Wellington V. Cardoso ◽  
...  
Keyword(s):  
Early Stage ◽  
Model Organism ◽  
Receptor Activation ◽  
Evolutionary Development ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Glucagon Receptor ◽  
Nutrient Deposition ◽  
Zebrafish Larvae

In mammals, glucose-dependent insulinotropic polypeptide (GIP) is synthesized predominately in the small intestine and functions in conjunction with insulin to promote nutrient deposition. However, little is known regarding GIP expression and function in early vertebrates like the zebrafish, a model organism representing an early stage in the evolutionary development of the compound vertebrate pancreas. Analysis of GIP and insulin ( insa) expression in zebrafish larvae by RT-PCR demonstrated that although insa was detected as early as 24 h postfertilization (hpf), GIP expression was not demonstrated until 72 hpf, shortly after the completion of endocrine pancreatic development but prior to the commencement of independent feeding. Furthermore, whole mount in situ hybridization of zebrafish larvae showed expression of GIP and insa in the same tissues, and in adult zebrafish, RT-PCR and immunohistochemistry demonstrated GIP expression in both the intestine and the pancreas. Receptor activation studies showed that zebrafish GIP was capable of activating the rat GIP receptor. Although previous studies have identified four receptors with glucagon receptor-like sequences in the zebrafish, one of which possesses the capacity to bind GIP, a functional analysis of these receptors has not been performed. This study demonstrates interactions between the latter receptor and zebrafish GIP, identifying it as a potential in vivo target for the ligand. Finally, food deprivation studies in larvae demonstrated an increase in GIP and proglucagon II mRNA levels in response to fasting. In conclusion, the results of these studies suggest that although the zebrafish appears to be a model of an early stage of evolutionary development of GIP expression, the peptide may not possess incretin properties in this species.

scholarly journals Effects of peptides derived from dietary proteins on mucus secretion in rat jejunum

2002 ◽  
Vol 283 (3) ◽  
pp. G521-G528 ◽  
Author(s):  
Jean Claustre ◽  
Férial Toumi ◽  
Aurélien Trompette ◽  
Gérard Jourdan ◽  
Henri Guignard ◽  
...  
Keyword(s):  
Casein Hydrolysate ◽  
Opioid Peptide ◽  
Receptor Activation ◽  
Opioid Antagonist ◽  
Maximal Response ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dietary Proteins ◽  
Rat Jejunum ◽  
Mucin Secretion ◽  
Mucin Release

The hypothesis that dietary proteins or their hydrolysates may regulate intestinal mucin discharge was investigated in the isolated vascularly perfused rat jejunum using an enzyme-linked immunosorbent assay for rat intestinal mucins. On luminal administration, casein hydrolysate [0.05–5% (wt/vol)] stimulated mucin secretion in rat jejunum (maximal response at 417% of controls). Lactalbumin hydrolysate (5%) also evoked mucin discharge. In contrast, casein, and a mixture of amino acids was without effect. Chicken egg albumin and its hydrolysate or meat hydrolysate also did not modify mucin release. Interestingly, casein hydrolysate-induced mucin secretion was abolished by intra-arterial TTX or naloxone (an opioid antagonist). β-Casomorphin-7, an opioid peptide released from β-casein on milk ingestion, induced a strong mucin secretion (response at 563% of controls) that was inhibited by naloxone. Intra-arterial β-casomorphin-7 also markedly increased mucin secretion (410% of controls). In conclusion, two enzymatic milk protein hydrolysates (casein and lactalbumin hydrolysates) and β-casomorphin-7, specifically, induced mucin release in rat jejunum. The casein hydrolysate-induced mucin secretion is triggered by a neural pathway and mediated by opioid receptor activation.

scholarly journals Emodin Improves Intestinal Health and Immunity through Modulation of Gut Microbiota in Mice Infected by Pathogenic Escherichia coli O1

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3314
Author(s):  
Ruijuan Gao ◽  
Chunjie Wang ◽  
Aricha Han ◽  
Yanping Tian ◽  
Shunan Ren ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Intestinal Microbiota ◽  
Goblet Cells ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Intestinal Mucosal Barrier ◽  
E Coli ◽  
Mucosal Barrier Function

The effect of emodin on the intestinal mucosal barrier of a mouse E. coli O1-induced diarrhea model was observed. Following successful establishment of a diarrhea model, the mice were treated with drugs for seven days. Intestinal lesions and the shape and the number of goblet cells were assessed via hematoxylin-eosin and periodic-acid-Schiff staining, while changes in inflammatory factors, ultrastructure of the small intestine, expression of MUC-2, and changes in the intestinal microbiota were analyzed via RT-PCR, electron microscopy, immunofluorescence, and 16S rRNA sequencing. Examination showed that emodin ameliorated pathological damage to the intestines of diarrheic mice. RT-PCR indicated that emodin reduced TNF-α, IL-β, IL-6, MPO, and COX-2 mRNA levels in duodenal tissues and increased the levels of sIgA and MUC-2 and the number of goblet cells. Microbiome analysis revealed that Escherichia coli O1 reduced bacterial richness and altered the distribution pattern of bacterial communities at the phylum and order levels in cecum contents. Notably, pathogenic Clostridiales and Enterobacteriales were significantly increased in diarrheic mice. However, emodin reversed the trend. Thus, emodin protected against intestinal damage induced by E. coli O1 and improved intestinal mucosal barrier function in mice by increasing the abundance of beneficial intestinal microbiota and inhibiting the abundance of harmful bacteria, thereby alleviating diarrhea.

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