Dissociated response of acid and pepsin secretion to omeprazole in an in vitro perfused mouse stomach

1984 ◽  
Vol 247 (3) ◽  
pp. G240-G247
Author(s):  
C. J. Fimmel ◽  
M. M. Berger ◽  
A. L. Blum
Keyword(s):  
Acid Secretion ◽  
Parietal Cell ◽  
Pepsin Secretion ◽  
Weak Base ◽  
Carbonyl Cyanide ◽  
Luminal Perfusion ◽  
Dose Dependent Fashion ◽  
K Concentration ◽  
Dose Dependent

The effect of omeprazole, an inhibitor of the parietal cell H+-K+-ATPase, on pepsin and acid secretion was studied in an in vitro perfused whole mouse stomach model. Omeprazole inhibited basal and dibutyryl cAMP (DBcAMP)- and histamine-stimulated acid secretion in a dose-dependent fashion with a maximally effective dose of 10(-4) M. At the same time, omeprazole induced a dose-dependent increase of unstimulated pepsin release. This increase was not affected by pretreatment with 10(-3) M atropine or 10(-4) M cimetidine. It was, however, inhibited by preincubation with 10(-4) M carbonyl cyanide m-chlorophenylhydrazone (CCCP). Pepsin secretion after maximally effective doses of histamine or DBcAMP was not affected by 10(-4) M omeprazole. In a concentration of 10(-5) M, the effect of omeprazole was additive to the effect of submaximal concentrations of carbachol and histamine. NaSCN and imidazole mimicked the effect of omeprazole on acid secretion, but pepsin release was only stimulated with 10(-2) M imidazole. Another weak base, benzylamine, stimulated acid and pepsin in parallel. Luminal perfusion with solutions of high K+ concentration did not enhance basal pepsin release. The dissociated response of acid and pepsin secretion indicates that omeprazole does not act selectively on the parietal cell. The stimulation of pepsin secretion might be related to the weak base properties of the compound.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Enhanced calcium signaling and acid secretion in parietal cells isolated from gastrin-deficient mice

2003 ◽  
Vol 284 (1) ◽  
pp. G145-G153 ◽  
Author(s):  
Karen L. Hinkle ◽  
Gina C. Bane ◽  
Ali Jazayeri ◽  
Linda C. Samuelson
Keyword(s):  
Acid Secretion ◽  
Parietal Cell ◽  
Mutant Cell ◽  
Flow Cytometric Analysis ◽  
Cell Number ◽  
Parietal Cells ◽  
Gastric Glands ◽  
Deficient Mice ◽  
Cell Defect

Gastrin-deficient mice have impaired basal and agonist-stimulated gastric acid secretion. To analyze whether an intrinsic parietal cell defect contributed to the reduced acid secretion, we analyzed parietal cell calcium responses and acid secretory function in vitro. Parietal cells were purified by light-scatter cell sorting and calcium responses to gastrin, histamine, and carbachol were measured in gastrin-deficient and wild-type mice cell preparations. Surprisingly, basal and histamine-induced calcium concentrations were higher in the mutant cell preparations. [14C]aminopyrine uptake analysis in acutely isolated gastric glands revealed that basal acid accumulation was enhanced in gastrin-deficient cell preparations as well as on treatment with carbachol or histamine. These results suggested that an intrinsic parietal cell defect was not responsible for the reduced acid secretion in gastrin-deficient mice. Flow cytometric analysis of dispersed, H+-K+-ATPase-immunostained gastric mucosal preparations revealed a marked increase in parietal cell number in gastrin-deficient mice, which may have accounted for the enhanced in vitro acid secretion detected in this study. Parietal cells were found to be significantly smaller in the mutant cell preparations, suggesting that gastrin stimulation modulates parietal cell morphology.

scholarly journals Relation of the CD11/CD18 family of leukocyte antigens to the transient neutropenia caused by chemoattractants

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1240-1245 ◽  
Author(s):  
C Lundberg ◽  
SD Wright
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Dose Dependence ◽  
Blood Stream ◽  
Leukocyte Antigens ◽  
Similar Dose ◽  
Inflammatory Site ◽  
Dose Dependent Fashion ◽  
Plasma Leakage ◽  
Dose Dependent

Abstract Adherence of leukocytes to the endothelium is a prerequisite for infiltration and accumulation of cells at an inflammatory site. Recent studies suggest that the CD11/CD18 family of adhesion-promoting receptors plays a crucial role in the initial adherence of polymorphonuclear leukocytes (PMNs) to endothelium. We have studied the effect of the anti-CD18 monoclonal antibody (MoAb) IB4, on movement of PMN in rabbits. Accumulation of PMNs in the skin induced by a local injection of the chemoattractant, zymosan-activated serum (ZAS), was strongly inhibited, in a dose-dependent fashion, by intravenous injection of IB4. A greater than 95% reduction in PMN accumulation was seen with 1 mg IB4/kg body weight, the highest dose used. PMN-dependent plasma leakage in the ZAS-injected skin sites was also inhibited by pretreatment with MoAb IB4, with a similar dose dependence. Histamine- induced plasma leakage, which is PMN independent, was not affected by this treatment. F(ab)2 fragments of IB4 were as effective as the whole immunoglobulin G molecule in reducing PMN accumulation. The half-life of circulating IB4 in rabbits was found to be 11.5 hours. These results are consistent with in vitro studies that show that binding of PMNs to endothelium requires both expression of CD11/CD18 molecules and activation of the PMNs by agonists, and confirm that sites on CD11/CD18 that recognize endothelial cells are blocked by IB4. Other investigators have shown that injection of chemoattractants into the blood stream causes a rapid neutropenia associated with accumulation of PMNs in the lung. We find that intravenous treatment of animals with IB4 did not block the transient accumulation of PMNs in the lung induced by formyl-methionyl-leucyl-phenylalanine, suggesting that this accumulation occurs by a mechanism that does not require CD11/CD18 molecules.

Ouabain reduces net acid secretion and increases pHi by inhibiting NH 4 + uptake on rat tIMCD Na+-K+-ATPase

1997 ◽  
Vol 273 (6) ◽  
pp. F857-F868 ◽  
Author(s):  
Susan M. Wall
Keyword(s):  
Acid Secretion ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Physiological Saline ◽  
Weak Base ◽  
Pump Activity ◽  
Total Ammonia ◽  
Medullary Collecting Duct ◽  
Saline Solutions

In the rat terminal inner medullary collecting duct (tIMCD), Na+ pump inhibition reduces transepithelial net acid secretion ( J tAMM) [ J H = total CO2 absorption ( J tCO2) + total ammonia secretion] and increases resting intracellular pH (pHi). The increase in pHi and reduction in J H that follow ouabain addition do not occur in the absence of[Formula: see text] nor when [Formula: see text]is substituted with another weak base. The purpose of this study was to explore the mechanism of the [Formula: see text]-dependent reduction in J tCO2 and increase in pHi that follow ouabain addition. We hypothesized that [Formula: see text]enters the tIMCD cell through the Na+-K+-ATPase with proton release in the cytosol. To test this hypothesis, tIMCDs were dissected from deoxycorticosterone-treated rats and perfused in vitro with symmetrical physiological saline solutions containing 6 mM NH4Cl. Since K+ and[Formula: see text] compete for a common binding site on the Na+ pump, increasing extracellular K+ should limit[Formula: see text] (and hence net H+) uptake by the Na+ pump. Upon increasing extracellular K+ concentration from 3 to 12 mM, the [Formula: see text]-dependent, ouabain-induced increase in pHiand reduction in J tCO2 were attenuated. In the presence but not in the absence of[Formula: see text], reducing Na+ pump activity by limiting Na+ entry reduced J tCO2 and attenuated ouabain-induced alkalinization. Ouabain-induced alkalinization was not dependent on the presence of[Formula: see text]/CO2and was not reproduced with BaCl2or bumetanide addition. Therefore, ouabain-induced alkalinization is not mediated by the Na+-K+-2Cl−cotransporter or a [Formula: see text] transporter and is not mediated by changes in membrane potential. In conclusion, on the basolateral membrane of the tIMCD cell,[Formula: see text] uptake is mediated by the Na+-K+-ATPase. These data provide an explanation for the reduction in net acid secretion in the tIMCD observed following administration of amiloride or with dietary K+ loading.

scholarly journals Effects of Caffeoylquinic Acid Derivatives and C-Flavonoid from Lychnophora ericoides on in vitro Inflammatory Mediator Production

2010 ◽  
Vol 5 (5) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Michel David dos Santos ◽  
Guanjie Chen ◽  
Maria Camila Almeida ◽  
Denis Melo Soares ◽  
Glória Emília Petto de Souza ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Cultured Cells ◽  
Dependent Manner ◽  
Caffeoylquinic Acid ◽  
Inflammatory Mediator Production ◽  
Dicaffeoylquinic Acid ◽  
Tnf Α ◽  
Dose Dependent Fashion ◽  
Dose Dependent

In this study we aimed at evaluating the effect of the major polar constituents of the medicinal plant Lychnophora ericoides on the production of inflammatory mediators produced by LPS-stimulated U-937 cells. The 6,8-di- C-β-glucosylapigenin (vicenin-2) presented no effect on tumor necrosis factor (TNF)-α production, but inhibited, in a dose-dependent manner, the production of prostaglandin (PG) E2 without altering the expression of cyclooxygenase (COX) -2 protein. 3,5-Dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid, at lower concentrations, had small but significant effects on reducing PGE2 levels; at higher doses these compounds stimulated PGE2 and also TNF-α production by the cells. All the caffeoylquinic acid derivatives, in a dose-dependent fashion, were able to inhibit monocyte chemoattractant protein-3 synthesis/release, with 4,5-DCQ being the most potent at the highest tested concentration. These results add important information on the effects of plant natural polyphenols, namely vicenin-2 and caffeoylquinic acid derivatives, on the production of inflammatory mediators by cultured cells.

Apamin, a highly specific Ca2+ blocking agent in heart muscle

1985 ◽  
Vol 248 (6) ◽  
pp. H961-H965 ◽  
Author(s):  
G. Bkaily ◽  
N. Sperelakis ◽  
J. F. Renaud ◽  
M. D. Payet
Keyword(s):  
Heart Muscle ◽  
Blocking Agent ◽  
Tyrode Solution ◽  
Tetraethylammonium Chloride ◽  
Naturally Occurring ◽  
Ventricular Cells ◽  
Dose Dependent Fashion ◽  
K Concentration ◽  
Dose Dependent ◽  
Slow Action Potentials

Apamin, a bee venom polypeptide, was recently reported to block specifically the Ca2+-dependent K+ channels that are not blocked by tetraethylammonium chloride in muscle cells. We report here that apamin blocked the naturally occurring slow action potentials (APs) in cultured cell reaggregates from chick hearts. The effects of apamin were not reversible on washout with Tyrode solution only (up to 24 h), but quinidine (10(-8) M) reversed the apamin blockade of the slow channels. Apamin also blocked the isoproterenol-induced slow APs in freshly isolated chick ventricular cells depolarized by 22 mM extracellular K+ concentration ([K+]o) in a dose-dependent fashion (10(-12) to 10(-10) M). Apamin at 5 X 10(-11) M blocked the isoproterenol-induced slow APs without affecting the membrane potential. Washout (with Tyrode solution containing 22 mM [K+]o and 10(-6) M isoproterenol) did not recover the slow APs. However, recovery of the slow APs was possible only when quinidine (10(-8) M) was added to the superfusion medium. The fast APs were rapidly restored by washout with Tyrode solution only. The present data show that apamin is a highly specific compound that tightly binds to the Ca2+ slow channels, thus blocking the slow APs in heart muscle. In addition, quinidine antagonizes the apamin binding on the slow APs.

Hyperpolarizing effect of aminophylline, theophylline, and cAMP on rat diaphragm fibers

1988 ◽  
Vol 64 (5) ◽  
pp. 1893-1899 ◽  
Author(s):  
O. Delbono ◽  
B. A. Kotsias
Keyword(s):  
Normal Values ◽  
Bath Temperature ◽  
Resting Membrane Potential ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Rat Diaphragm ◽  
K Concentration ◽  
Dose Dependent ◽  
K Permeability

We studied the effect of aminophylline and theophylline (0.1–2 mM) on the resting membrane potential (Vm) of rat diaphragm fibers in vitro (25 degrees C). The main findings are the following. 1) Aminophylline and theophylline hyperpolarize the fibers in a dose-dependent manner. This effect is present with 0.1 and 0.25 mM of aminophylline and theophylline, respectively, and the maximum effect is reached with 1 mM of the drug (approximately 5–8 mV in comparison to the normal values). This effect is reversible by washing out the preparation with normal solution. 2) Dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP, 2 mM) produces a similar increment in the Vm. 3) The hyperpolarizing action observed in the presence of aminophylline, theophylline, and DBcAMP is suppressed by 5 X 10(-4) M ouabain or by lowering the bath temperature to 5 degrees C. These results suggest that the xanthines may directly or indirectly stimulate a Na-K pump. Two possibilities may be considered: 1) an electrogenic effect of the Na-K pump and 2) a reduction in the extracellular K+ concentration in the solution contacting the external side of the cell as a consequence of the activity of the Na-K pump. Alternative mechanisms such as a reduction in Na permeability or an increment in K permeability might collaborate in the hyperpolarizing effect of the drugs tested.

cAMP-stimulated rise of [Ca2+]i in rabbit connecting tubules: role of peritubular Ca

1990 ◽  
Vol 258 (3) ◽  
pp. F751-F755 ◽  
Author(s):  
J. E. Bourdeau ◽  
B. K. Eby
Keyword(s):  
Parathyroid Hormone ◽  
Ethylene Glycol ◽  
Cell Activation ◽  
Proximal Tubules ◽  
Tetraacetic Acid ◽  
Luminal Membrane ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Parathyroid hormone (PTH) increases cytosolic free Ca concentration ([ Ca2+]i) by mechanisms that depend on extracellular Ca in both cultured renal proximal tubules and isolated rabbit connecting tubules (CNTs). In CNTs 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) mimics this action, implicating cAMP as a second messenger, and part of the rise, due to increased luminal membrane Ca entry, is likely related to Ca absorption. In cultured proximal tubules the rise in [Ca2+]i, presumably mediated by increased Ca entry across the basolateral plasmalemma, activates gluconeogenesis and shortens microvilli. In the present study we examined cAMP-mediated Ca entry across the basolateral membranes of CNT cells, an effect potentially related to cell activation. Single CNTs were dissected from rabbit kidneys and loaded with fura-2. [Ca2+]i was measured by dual-wavelength excitation during perfusion of isolated segments in vitro. With 1.8 or 2.0 mM Ca in the lumen and the bath, suffusate 8-BrcAMP increased [Ca2+]i within minutes in a dose-dependent fashion. The increase persisted as long as 8-BrcAMP was present and reversed on its withdrawal. With 0.1 microM Ca in the lumen and the bath, 8-BrcAMP, but not ionomycin, failed to increase [Ca2+]i, implying that extracellular Ca is the major source. In tubules perfused with 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid to eliminate luminal Ca, but suffused with 1.8 or 2.0 mM Ca, 8-BrcAMP increased [Ca2+]i (though less so than with Ca in the lumen), implying Ca entry across basolateral cell membranes. This rise in [Ca2+]i was attenuated markedly by the presence of 50 microM LaCl3 in the bath.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals A Cumulative Spore Killing Approach: Synergistic Sporicidal Activity of Dilute Peracetic Acid and Ethanol at Low pH Against Clostridium difficile and Bacillus subtilis Spores

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Michelle M. Nerandzic ◽  
Thriveen Sankar C ◽  
Peter Setlow ◽  
Curtis J. Donskey
Keyword(s):  
Bacillus Subtilis ◽  
Clostridium Difficile ◽  
Peracetic Acid ◽  
Water Washing ◽  
Healthcare Settings ◽  
Synergistic Enhancement ◽  
Spore Killing ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Abstract Background.  Alcohol-based hand sanitizers are the primary method of hand hygiene in healthcare settings, but they lack activity against bacterial spores produced by pathogens such as Clostridium difficile and Bacillus anthracis. We previously demonstrated that acidification of ethanol induced rapid sporicidal activity, resulting in ethanol formulations with pH 1.5–2 that were as effective as soap and water washing in reducing levels of C difficile spores on hands. We hypothesized that the addition of dilute peracetic acid (PAA) to acidified ethanol would enhance sporicidal activity while allowing elevation of the pH to a level likely to be well tolerated on skin (ie, >3). Methods.  We tested the efficacy of acidified ethanol solutions alone or in combination with PAA against C difficile and Bacillus subtilis spores in vitro and against nontoxigenic C difficile spores on hands of volunteers. Results.  Acidification of ethanol induced rapid sporicidal activity against C difficile and to a lesser extent B subtilis. The addition of dilute PAA to acidified ethanol resulted in synergistic enhancement of sporicidal activity in a dose-dependent fashion in vitro. On hands, the addition of 1200–2000 ppm PAA enhanced the effectiveness of acidified ethanol formulations, resulting in formulations with pH >3 that were as effective as soap and water washing. Conclusions.  Acidification and the addition of dilute PAA induced rapid sporicidal activity in ethanol. Our findings suggest that it may be feasible to develop effective sporicidal ethanol formulations that are safe and tolerable on skin.

Differential effects of [Gln4]neurotensin on circular and longitudinal muscle of dog ileum in vitro

1987 ◽  
Vol 253 (4) ◽  
pp. G566-G572
Author(s):  
M. Karaus ◽  
K. R. Prasad ◽  
S. K. Sarna ◽  
I. M. Lang
Keyword(s):  
Longitudinal Muscle ◽  
Contractile Activity ◽  
Circular Muscle ◽  
Electrical Field Stimulation ◽  
Cholinergic Nerves ◽  
Differential Effects ◽  
Dose Dependent Fashion ◽  
Dose Dependent ◽  
Muscle Contractile

We studied the effects of neurotensin analogue [Gln4]-neurotensin on isolated dog ileal longitudinal and circular muscle strips. [Gln4]neurotensin stimulated the spontaneous contractile activity of the circular muscle but inhibited that of the longitudinal muscle in a dose-dependent fashion. Hexamethonium had no effect on the spontaneous longitudinal or circular muscle contractile activity. Atropine and tetrodotoxin (TTX) both inhibited the longitudinal muscle. Atropine had no effect on the circular muscle, but TTX stimulated it. The effects of [Gln4]neurotensin on the circular muscle were reduced but not completely abolished by atropine. The inhibition of the longitudinal muscle by [Gln4]neurotensin was not reduced by any of the above antagonists but was enhanced by atropine. Electrical field stimulation (10 Hz, 100 mA) stimulated the longitudinal muscle and inhibited or stimulated the circular muscle depending on the pulse width of the stimulus. These effects were unaffected by [Gln4]neurotensin. We conclude that [Gln4]neurotensin has differential effects on isolated muscle strips of the two muscle layers in the dog ileum. It stimulates the circular muscle partially through cholinergic nerves at preganglionic sites and partially through a direct myogenic effect. [Gln4]neurotensin inhibits the spontaneous activity of the longitudinal muscle presumably by reducing the excitability of cholinergic nerves at postganglionic sites.

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