The effects of indomethacin on calcium, sodium, potassium and magnesium fluxes in various tissues of the guinea‐pig

Northover, B. J.

doi:10.1111/j.1476-5381.1972.tb08124.x

Cited by 53 publications

(25 citation statements)

References 19 publications

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“…Since some of the tissue stores of Ca are bound to cell membranes (Bianchi, 1968) it was of interest to examine whether indomethacin reduces the binding of Ca to cellular and subcellular membranes and whether the drug is more effective on membranes derived from smooth muscle cells than those derived from other tissues of the guinea-pig. It has been suggested that the ability of indomethacin to reduce the uptake of Ca by damaged tissues may be related to its anti-inflammatory activity (Northover, 1972). It was of interest, therefore, to determine whether other nonsteroidal anti-inflammatory drugs inhibit the binding of Ca to cell membranes.…”

Section: Introductionmentioning

confidence: 99%

“…Addition of indomethacin to the bathing fluid inhibited the electricallyinduced uptake of Ca and Na both by aorta and by gastric smooth muscle, but failed to alter the fluxes of these elements in brain, myocardium or skeletal muscle (Northover, 1971(Northover, , 1972. Since some of the tissue stores of Ca are bound to cell membranes (Bianchi, 1968) it was of interest to examine whether indomethacin reduces the binding of Ca to cellular and subcellular membranes and whether the drug is more effective on membranes derived from smooth muscle cells than those derived from other tissues of the guinea-pig.…”

Section: Introductionmentioning

confidence: 99%

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Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues

Northover

1973

British J Pharmacology

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Summary1. Cellular membranes were obtained by centrifugation of homogenates of various human and guinea-pig tissues. These membranes took up added calcium (Ca) when incubated at 250 C for 10 min in histidine buffer at pH 7-4. The uptake of Ca was increased by the presence of adenosine triphosphate (ATP).2. Evidence is presented that the membrane fragments which took up Ca under these conditions were derived from the endoplasmic reticulum. 3. The ATP-dependent uptake of Ca by membranes derived from guinea-pig aortic or gastric smooth muscle or from human umbilical arterial muscle was inhibited by indomethacin in a concentration-dependent manner. 4. The ATP-dependent uptake of Ca by membranes derived from heart, brain, skeletal muscle or liver of the guinea-pig was not inhibited by indomethacin. 5. Endothelial cells were obtained from the lining of the human umbilical vein. Cellular membranes were prepared from the endothelial cells by homogenization and centrifugation. The endothelial membranes took up added Ca in the presence of added ATP and this uptake was inhibited by indomethacin and also by members of a group of pharmacologically-related drugs.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues

Northover

1973

British J Pharmacology

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“…Indomethacin is known to produce its action on various tissues via an inhibition of the biosynthesis of prostaglandins at concentrations of 2.8 x 10-q to 1.4 x 10-s M (11), while at higher concentrations a nonspecific inhibitory action has been reported (12)(13).…”

Section: Effects Of Metabolic Depletion On the Vrcmentioning

confidence: 99%

Rhythmic Contractions Induced by Vagotomy in the Fundus of Rat Stomach

Kamata

Watanabe

Kasuya

1979

Japanese Journal of Pharmacology

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Abstract-Continuous rhythmic contractions were observed in longitudinal muscle strips of fundus obtained from the chronically vagotomized rat stomach. These vagotomy-induced rhythmic contractions (VRC) were not blocked either by tetro dotoxin (3 x 10-6 M) or atropine (3 x 10_1 M), indicating that the VRC was myogenic in origin. It was also found that the VRC had the following characteristics.1) The VRC was blocked either by 10-5 M D600 or by Ca 2+ deprivation from the medium. 2) On replacement of Na+ with sucrose or of K` with Na+, the tone of fundus strips was concomitantly elevated with the cessation of the VRC. 3) 10-5 M ouabain blocked the VRC. 4) The VRC was blocked by cooling. 5) The VRC disappeared under anoxic conditions. Based on these results possible mechanisms of the VRC are dis cussed in relation to an energy dependent activity of the cell membrane.Among the smooth muscle from different tissues which exhibit rhythmic spontaneous contractions in vitro are those from the taenia coli, portal vein, etc. These spontaneous activities seem to be myogenic in origin, since various drugs which interefere with the nervous activity or transmission do not abolish the activities (1-3).On the other hand, rat stomach fundus strips free of mucosa show no spontaneous mechanical activity under usual conditions in vitro (4). In a previous paper, however, we reported that when fLindus strips were prepared from chronically vagotomized rat stomach they exhibited spontaneous rhythmic contractions and that their maximum contractile responses to cholinergic agonists and to serotonin decreased to an appreciable extent. These findings suggest that vagotomy exerts a profound influence on smooth muscle activities (5).This study was undertaken to obtain insight into the mechanisms underlying the spon taneous rhythmic contractions. For this purpose the effects of some agents, of deprivation of ions from the bathing fluid, and also of chronic sympathectomy were investigated. MATERIALS AND METHODSMale rats of Donryu strain weighing from 240 to 300 g were used.Chronic sympa thectomy was performed by excision of celiac ganglion and some length of postganglionic nerve bundle as reported previously (5). Chronic vagotomy was performed by bilateral

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“…Indomethacin and some pharmacologically related drugs reduce the uptake of calcium by electrically stimulated smooth muscle (Northover, 1972). Adenosine triphosphate-dependent binding of calcium to microsomes derived from smooth muscle or vascular endothelium is also inhibited by these drugs (Northover, 1973).…”

Section: Introductionmentioning

confidence: 99%

EFFECT OF ANTI‐INFLAMMATORY DRUGS ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro

Northover

1975

British J Pharmacology

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1Cells of the aortic endothelium isolated from the guinea-pig and bathed at 370 C with a calcium-free superfusion fluid had membrane potentials of -41 ± 7 mV (mean ± s.e. mean). 2 Depolarization was produced by addition of potassium (50-200 mM) 6 Exposure to histamine (100 jig/ml) or heating to 450 C for 1 h caused depolarization in the presence but not in the absence of calcium. Subsequent removal of histamine or cooling again to 370 C in the continued presence of calcium permitted only slow and partial repolarization. However, repolarization was more rapid and complete in the presence of indomethacin (0.25 mM). 7 Heating to 450 C for 5 h in the presence of calcium caused progressive and almost complete depolarization. Lanthanum, cinchocaine, indomethacin, flufenamic, meclofenamic and salicylic acids, phenylbutazone and aminopyrine each reduced the depolarization, but hydrocortisone, chloroquine, benzindamine, isoprenaline and aminophylline did not.

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The effects of indomethacin on calcium, sodium, potassium and magnesium fluxes in various tissues of the guinea‐pig

Cited by 53 publications

References 19 publications

Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues

Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues

Rhythmic Contractions Induced by Vagotomy in the Fundus of Rat Stomach

EFFECT OF ANTI‐INFLAMMATORY DRUGS ON THE MEMBRANE POTENTIAL OF VASCULAR ENDOTHELIAL CELLS in vitro

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