Cardiac antisecretory peptide inhibits intestinal chloride secretion

1989 ◽  
Vol 257 (4) ◽  
pp. C775-C780 ◽  
Author(s):  
S. M. O'Grady ◽  
P. J. Wolters

A heat-stable low-molecular-weight peptide isolated from porcine heart inhibited vasoactive intestinal polypeptide and ionomycin (a Ca ionophore) -stimulated Cl secretion across the rat ileum. The antisecretory effects of this peptide were resistant to the neuronal conduction blocker tetrodotoxin, suggesting that submucosal nerves were not involved in mediating its effects on Cl transport. Activity was found in extracts of the right and left atria and in the ventricles of the heart. The antisecretory effect was not mimicked by atrial natriuretic factor, brain natriuretic peptide, or by putative antisecretory factors (neuropeptide Y, somatostatin, enkephalin, and norepinephrine), suggesting that cardiac antisecretory peptide is a unique regulatory factor that may regulate Cl transport in the intestinal mucosa and other epithelia.

1995 ◽  
Vol 268 (6) ◽  
pp. R1411-R1417
Author(s):  
D. Javeshghani ◽  
S. Mukaddam-Daher ◽  
L. Fan ◽  
Z. Guan ◽  
J. Gutkowska ◽  
...  

Previous studies of the atrial stretch-atrial natriuretic factor (ANF) relationship during pregnancy have employed volume expansion and measured only right atrial pressure (RAP). Consequently, we studied nonpregnant (n = 7) and 115- to 125-day pregnant (n = 7) sheep and assessed the ANF response to changes of RAP and left atrial pressure (LAP) induced by graded balloon inflation. Ewes prepared with vascular catheters and atrial balloons were studied after recovery from preparatory surgical procedures. The basal levels of mean arterial pressure (MAP, 83 +/- 3 mmHg), RAP (2.1 +/- 0.7 mmHg), LAP (4.7 +/- 0.9 mmHg), and heart rate (HR, 102 +/- 6 beats/min) were similar in nonpregnant and pregnant sheep. Pregnancy also resulted in elevation of ANF concentration from 25 +/- 6 to 57 +/- 4 fmol/ml. With right atrial distension, the RAP-ANF relationships were similar in both nonpregnant and pregnant sheep, with a 10-mmHg increase in RAP increasing ANF by an average of 95 +/- 9 fmol/ml. In nonpregnant sheep, the LAP-ANF relationship was more responsive than RAP-ANF because a 10-mmHg increase in LAP resulted in a 193 +/- 10 fmol/ml increase in ANF. Moreover, during pregnancy, the LAP-ANF relationship was significantly more sensitive because a 10-mmHg increase in LAP resulted in a 433 +/- 15 fmol/ml elevation of ANF. These data demonstrate that plasma ANF levels are more responsive to distension of the left atria than to the right. More importantly, the ANF response to left, but not right, atrial distension is enhanced by pregnancy.


2015 ◽  
Vol 96 (12) ◽  
pp. 3587-3597 ◽  
Author(s):  
Timothy J. Green ◽  
Peter Speck ◽  
Lu Geng ◽  
David Raftos ◽  
Michael R. Beard ◽  
...  

Little is known about the response of non-model invertebrates, such as oysters, to virus infection. The vertebrate innate immune system detects virus-derived nucleic acids to trigger the type I IFN pathway, leading to the transcription of hundreds of IFN-stimulated genes (ISGs) that exert antiviral functions. Invertebrates were thought to lack the IFN pathway based on the absence of IFN or ISGs encoded in model invertebrate genomes. However, the oyster genome encodes many ISGs, including the well-described antiviral protein viperin. In this study, we characterized oyster viperin and showed that it localizes to caveolin-1 and inhibits dengue virus replication in a heterologous model. In a second set of experiments, we have provided evidence that the haemolymph from poly(I : C)-injected oysters contains a heat-stable, protease-susceptible factor that induces haemocyte transcription of viperin mRNA in conjunction with upregulation of IFN regulatory factor. Collectively, these results support the concept that oysters have antiviral systems that are homologous to the vertebrate IFN pathway.


Author(s):  
Syahfori Widiyani ◽  
Irsalina Rahmawati ◽  
W. Yohannes Widodo ◽  
Dian Zamroni ◽  
Fajar L. Gultom ◽  
...  

Introduction: Bullous haemorrhagic dermatosis is a rare clinical disorder which is usually related to a treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH), characterized by multiple intra-epidermal haemorrhages distant from the site of injection. Presentation of Case: A 62-year-old male patient with coronary heart disease who received heparin treatment experienced several tense, haemorrhagic bullae located on the right arm area, close to the injection site, and followed by the formation of several hematomas on his back trunk 2 days after he had received UFH. The lesions regressed after discontinuation of heparin and supportive topical treatments. Discussion: The lesions in this patient have similar characteristic with heparin-induced skin necrosis and demonstrate thrombocytopenia probably related to heparin. There are some proposed hypotheses of pathophysiology which include hypersensitivity reaction and idiosyncratic dose-related reaction. Given the clinically course, the discontinuation of heparin treatment was essential for lesion regression in addition other supportive measures. Conclusion: Heparin-induced skin lesions may indicate the presence of life-threatening heparin-induced thrombocytopenia. An early diagnosis is crucial to enable discontinuation of heparin if required.


1994 ◽  
Vol 266 (5) ◽  
pp. G899-G906 ◽  
Author(s):  
D. W. Laney ◽  
J. A. Bezerra ◽  
J. L. Kosiba ◽  
S. J. Degen ◽  
M. B. Cohen

Guanylate cyclase C (GC-C) is a transmembrane protein that serves as a receptor for the recently characterized endogenous ligand guanylin and for Escherichia coli heat-stable toxin (STa). Binding of either guanylin or STa to intestinal GC-C results in net chloride secretion. Although GC-C is expressed in the rat intestine throughout life, its expression in the rat liver has previously been shown to occur only during the perinatal period. As a step toward elucidating the role of this receptor in the liver, we tested the hypothesis that GC-C mRNA expression could be induced in the adult rat liver following 1) partial hepatectomy, a stimulus for hepatocyte proliferation; 2) intraperitoneal carbon tetrachloride injection, a model of hepatocyte regeneration in the presence of inflammatory changes; and 3) subcutaneous turpentine injection, which generates an acute phase response without hepatocyte proliferation. We demonstrated expression of GC-C mRNA in the regenerating rat liver following either partial hepatectomy or CCl4-induced hepatic necrosis. We have also shown that GC-C mRNA expression occurred in association with an acute phase reaction. Coordinate with the expression of GC-C mRNA, there was upregulation of radiolabeled STa binding to liver plasma membranes prepared from turpentine-treated rats. Maximal expression of GC-C occurred in preparations enriched for the canalicular domain. Although the function of GC-C in the liver is unknown, localization to the canalicular domain would be consistent with a role for GC-C in hepatic chloride secretion, especially in the perinatal liver and during hepatocyte regeneration.


1991 ◽  
Vol 260 (6) ◽  
pp. G904-G910 ◽  
Author(s):  
K. J. Goerg ◽  
C. Diener ◽  
M. Diener ◽  
W. Rummel

The effect of prostaglandin D2 (PGD2) on colonic ion transport was studied in the Ussing chamber. PGD2 (10(-6) M) decreased baseline short-circuit current (Isc) in two preparations of rat colon descendens, a mucosa-submucosa preparation with and a mucosa preparation without the submucosal plexus. In both preparations, PGD2 inhibited the neuronally mediated secretory responses to electric field stimulation, the sea anemone toxin ATX II, and different cholinergic agents. Unidirectional flux measurements revealed that PGD2 diminished the secretagogue-induced increase in the serosal-to-mucosal flux of Cl- and thereby inhibited net Cl- secretion. PGD2, however, had no effect on the adenosine 3',5'-cyclic monophosphate-mediated response to forskolin or vasoactive intestinal peptide or on guanosine 3',5'-cyclic monophosphate-mediated secretion induced by the heat-stable enterotoxin of Escherichia coli. The PGD2 also blocked the increase in Isc evoked by two neuronally acting inflammatory mediators, i.e., bradykinin and PGI2 in the mucosa-submucosa preparation, but had no effect on the response to PGE2. Consequently, PGD2 exerts an indirect antisecretory effect caused by an inhibition of enteric secretomotor neurons of both the submucosal and the mucosal plexus.


2007 ◽  
Vol 292 (5) ◽  
pp. C1906-C1914 ◽  
Author(s):  
Aliye Uc ◽  
Krzysztof J. Reszka ◽  
Garry R. Buettner ◽  
John B. Stokes

Heme induces Cl− secretion in intestinal epithelial cells, most likely via carbon monoxide (CO) generation. The major source of endogenous CO comes from the degradation of heme via heme oxygenase (HO). We hypothesized that an inhibitor of HO activity, tin protoporphyrin (SnPP), may inhibit the stimulatory effect of heme on Cl− secretion. To test this hypothesis, we treated an intestinal epithelial cell line (Caco-2 cells) with SnPP. In contrast to our expectations, Caco-2 cells treated with SnPP had an increase in their short-circuit currents ( Isc) in Ussing chambers. This effect was observed only when the system was exposed to ambient light. SnPP-induced Isc was caused by Cl− secretion because it was inhibited in Cl−-free medium, with ouabain or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). The Cl− secretion was not via activation of the CFTR, because a specific inhibitor had no effect. Likewise, inhibitors of adenylate cyclase and guanylate cyclase had no effect on the enhanced Isc. SnPP-induced Isc was inhibited by the antioxidant vitamins, α-tocopherol and ascorbic acid. Electron paramagnetic resonance experiments confirmed that oxidative reactions were initiated with light in cells loaded with SnPP. These data suggest that SnPP-induced effects may not be entirely due to the inhibition of HO activity but rather to light-induced oxidative processes. These novel effects of SnPP-photosensitized oxidation may also lead to a new understanding of how intestinal Cl− secretion can be regulated by the redox environment of the cell.


1954 ◽  
Vol 32 (1) ◽  
pp. 400-406 ◽  
Author(s):  
M. O. Burton ◽  
F. J. Sowden ◽  
A. G. Lochhead

A procedure is described for the production and concentration of the 'terregens factor' (TF), a bacterial growth promoting substance synthesized by Arthrobacter pascens and essential for the growth of Arthrobacter terregens. From culture filtrates of A. pascens cultivated in a medium of inorganic salts and sucrose, concentrates of TF may be obtained that are active at 0.001 μgm. Per ml., heat stable and contain about 12.7% nitrogen. Acid hydrolysis yielded a number of amino acids, including glutamic acid, glycine, α–alanine, valine, leucine, proline, lysine, and arginine, as well as some unidentified compounds; however, TF does not appear to be a low molecular weight straight chain peptide.Although TF contains no iron, it combines readily with ferrous or ferric iron to form reddish-brown complexes with this metal. Activity for A. terregens is shown by certain iron containing complexes as hemin, coprogen, and ferrichrome. On the other hand none is shown by cytochrome or pulcherrimin; however, aspergillic acid, structurally related to the latter, possesses some growth promoting activity for the test organism.


1984 ◽  
Vol 247 (3) ◽  
pp. R610-R613 ◽  
Author(s):  
A. T. Veress ◽  
H. Sonnenberg

We have shown previously that an extract of atrial tissue from rat heart contains a potent natriuretic factor. In this study anesthetized rats were connected to a respirator and the right atrial appendage was either excised, using a loop ligature (experimental group), or the loop was placed around the appendage and then removed (sham-operated group). After equilibration and control urine collection periods an isooncotic Ringers-albumin solution was infused intravenously (25% of estimated blood volume), and renal function was monitored over the next hour. There were no differences between groups in control period arterial or central venous pressures, heart rates, cardiac outputs, renal blood flows, or filtration rates. However, the diuretic and natriuretic responses to infusion in the experimental group were only one half of those in the sham-operated series (vol = 23.4 +/- 6.2 vs. 68.2 +/- 11.0 microliter X min-1 X g kidney wt-1, UNa V = 2,731 +/- 856 vs. 6,504 +/- 962 nmol X min-1 X g kidney wt-1). These differences were not affected by prior bilateral vagotomy. Administration of homologous atrial natriuretic factor or furosemide resulted in identical renal responses in both groups. We conclude therefore that acute hypervolemia is associated with release of atrial natriuretic factor into the bloodstream and that removal of the atrial appendage reduces the amount available for such release.


1987 ◽  
Vol 253 (6) ◽  
pp. G775-G780 ◽  
Author(s):  
A. Guarino ◽  
M. Cohen ◽  
M. Thompson ◽  
K. Dharmsathaphorn ◽  
R. Giannella

Escherichia coli heat-stable enterotoxin (STa) induces intestinal secretion by binding to enterocyte receptors and activating the guanylate cyclase-guanosine 3',5'-cyclic monophosphate (cGMP) system. The intermediate steps between binding of STa and secretion are poorly understood, due in part to the lack of a convenient system to study the effects of STa at the cellular level. To establish such a model, we investigated the binding of 125I-STa, STa activation of guanylate cyclase, and STa-induced increase in cGMP production in a well-characterized human colonic cell line, T84. Binding was specific, linear with cell number, and time, temperature and pH dependent, and reversible. ST may also be internalized by these cells. Addition of unlabeled STa competitively inhibited binding of 125I-STa. These parameters closely resemble those described in intact rat enterocytes and cell-free membrane preparations. STa stimulated guanylate cyclase and cGMP production in a dose-related manner. The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors. These data, together with the fact that STa induces chloride secretion from T84 cells suggest that T84 cells are a suitable and convenient system to study the cellular mechanism of action of STa.


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