Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5–500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1–10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

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Dose-dependent inhibition of phosphoinositide metabolism in human platelets by aspirin in vitro and in vivo.

British Journal of Clinical Pharmacology ◽

10.1111/j.1365-2125.1986.tb02915.x ◽

1986 ◽

Vol 22 (4) ◽

pp. 443-447 ◽

Cited By ~ 3

Author(s):

PP Godfrey ◽

F Bochner ◽

DG Grahame-Smith

Keyword(s):

Human Platelets ◽

Phosphoinositide Metabolism ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent

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Nickel inhibits endothelin-induced contractions of vascular smooth muscle

AJP Cell Physiology ◽

10.1152/ajpcell.1990.258.6.c1025 ◽

1990 ◽

Vol 258 (6) ◽

pp. C1025-C1030 ◽

Cited By ~ 40

Author(s):

K. Blackburn ◽

R. F. Highsmith

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Isometric Force ◽

Inhibitory Effect ◽

Rat Aorta ◽

Porcine Coronary Artery ◽

Force Development ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent

Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.

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LINEAR DOSE-DEPENDENT INHIBITION OF TAU AGGREGATION IN VIVO WITH SMALL MOLECULE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2019.09.062 ◽

2019 ◽

Vol 15 (7) ◽

pp. P1599

Author(s):

James G. Moe ◽

Patricia Lopez ◽

Heidy Jimenez ◽

Leslie Adrien ◽

Peter Davies ◽

...

Keyword(s):

Small Molecule ◽

Linear Dose ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Tau Aggregation ◽

Dose Dependent

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Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.5.h1836 ◽

1998 ◽

Vol 274 (5) ◽

pp. H1836-H1840 ◽

Cited By ~ 21

Author(s):

Xiaofa Qin ◽

Debi K. Swertfeger ◽

Shuqin Zheng ◽

David Y. Hui ◽

Patrick Tso

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Inhibitory Effect ◽

Lipoprotein Oxidation ◽

Atherogenic Lipid Profile ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Endogenous Antioxidant ◽

Knockout Animals

Overexpression of apolipoprotein (apo) AIV in transgenic mice confers significant protection against atherosclerosis in apoE knockout animals even in the presence of a more severe atherogenic lipid profile. Because lipoprotein oxidation has been recognized to be pivotal in development of atherosclerosis, the antioxidative activity of apoAIV was investigated. Fasting intestinal lymph was used to mimic conditions in the interstitial fluid, the potential site for lipoprotein oxidation in vivo. ApoAIV (10 μg/ml) significantly inhibited copper-mediated oxidation of lymph. This inhibitory effect was further evaluated using purified low-density lipoprotein. Addition of apoAIV (2.5 μg/ml) increased the time of 50% conjugated diene formation by 2.4-fold, whereas apoE or BSA did not show such a protection even at 20 μg/ml. Addition of apoAIV during the propagation phase also resulted in a dose-dependent inhibition. ApoAIV also protected macrophage-induced oxidation of fasting lymph. These results provide the first evidence that apoAIV is a potent endogenous antioxidant.

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Eicosanoids are modulators of larval settlement in the barnacle, Balanus amphitrite

Journal of the Marine Biological Association of the United Kingdom ◽

10.1017/s0025315499001629 ◽

1999 ◽

Vol 80 (1) ◽

pp. 113-117 ◽

Cited By ~ 13

Author(s):

John Knight ◽

Andrew F. Rowley ◽

Mizue Yamazaki ◽

Anthony S. Clare

Keyword(s):

High Performance ◽

Larval Settlement ◽

Nordihydroguaiaretic Acid ◽

Balanus Amphitrite ◽

Lipoxygenase Inhibitors ◽

Lipoxygenase Products ◽

Dependent Inhibition ◽

Generating Capacity ◽

Dose Dependent Inhibition ◽

Dose Dependent

Eicosanoids are oxygenated derivatives of C20 polyunsaturated fatty acids known to play key roles in many physiological events in both invertebrates and vertebrates. The eicosanoid generating capacity of cypris larvae of the barnacle, Balanus amphitrite, was examined using enzyme immunoassay and high-performance liquid chromatography. These larvae generated the lipoxygenase products, 12-hydroxyeicosapentaenoic acid (HEPE), 8-HEPE and 8,15-diHEPE, together with the cyclooxygenase products, prostaglandin (PG) E, PGF and thromboxane (TX) B. Indomethacin, a selective cyclooxygenase inhibitor, caused a dose-dependent inhibition of PGE generation by B. amphitrite larvae, while esculetin and nordihydroguaiaretic acid (lipoxygenase inhibitors) also strongly inhibited the generation of 8-HEPE, 12-HEPE and 8,15-diHEPE. PGE2, PGE3 and 16,16-dimethyl PGE2 caused a dose-dependent inhibition of settlement of B. amphitrite larvae while indomethacin (25–100 μM) stimulated this process. Lipoxygenase products (8-HEPE, 12-HEPE and 8,15-diHEPE) as well as esculetin and nordihydroguaiaretic acid (10–100 μM) had no effect on the attachment of larvae.

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Coupling In vitro and In vivo Paradigm Reveals a Dose Dependent Inhibition of Angiogenesis Followed by Initiation of Autophagy by C6-Ceramide

International Journal of Biological Sciences ◽

10.7150/ijbs.7.629 ◽

2011 ◽

Vol 7 (5) ◽

pp. 629-644 ◽

Cited By ~ 18

Author(s):

Rishipal R. Bansode ◽

Mohamed Ahmedna ◽

Kurt R. Svoboda ◽

Jack N. Losso

Keyword(s):

Dependent Inhibition ◽

Inhibition Of Angiogenesis ◽

C6 Ceramide ◽

Dose Dependent Inhibition ◽

Dose Dependent

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Antigenic Reactivity of Peptides Derived from Wheat Gluten with Sera from Patients with Coeliac Disease

Clinical Science ◽

10.1042/cs0690097 ◽

1985 ◽

Vol 69 (1) ◽

pp. 97-104 ◽

Cited By ~ 5

Author(s):

P. M. Rawcliffe ◽

J. D. Priddle ◽

D. P. Jewell

Keyword(s):

Coeliac Disease ◽

Wheat Gluten ◽

Gel Filtration ◽

Enzyme Linked Immunosorbent Assay ◽

Jejunal Mucosa ◽

Active Inhibitor ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Dose Dependent ◽

Peptide Fractions

1. Fraction B from a peptic-tryptic digest of gluten from Scout 66 wheat has already been shown to cause histological damage to the jejunal mucosa of coeliac patients. Peptide fractions, designated P1-P4, have been prepared from it by a combination of gel filtration (producing an intermediate fraction pseudo-B2: ψ B2) and reverse-phase high pressure liquid chromatography. 2. An enzyme-linked immunosorbent assay (ELISA) has been used to measure IgG antibodies to fraction B in sera from untreated coeliac patients, patients with inflammatory bowel disease (IBD) and healthy individuals. The coeliac group had significantly higher (P < 0.05) antibody levels to fraction B than either of the control groups [medians: coeliac disease (n = 21), 0.247; IBD (n = 17) 0.019; healthy controls (n = 13) 0.020]. Five coeliac sera which gave high absorbance values in the ELISA were chosen and pre-incubated with fraction B in a range of concentrations, before assay by ELISA: a dose-dependent inhibition of binding was found. 3. Two sera which gave high ELISA values were preincubated with fractions B2 and P1-P4. B2, P1, P2 and P4 gave a dose-dependent inhibition, with P1 being the most potent. Absolute values were different for the two sera but the same relative pattern of reactivity was observed for each. With the serum giving the higher ELISA value the concentration of fraction (μg/ml) giving a 50% inhibition of binding when 0.5 ml was added to 0.5 ml of a 1/500 dilution of the serum (IC50) was 2.6 for fraction B, 61 for P1, 155 for B2 and 285 and 295 for P4 and P2 respectively. Fraction P3 had negligible inhibitory effect at the doses tested. With the second serum, P1 was again the most active inhibitor. 4. It is concluded that different peptide fractions of wheat gluten have differing reactivity with antibodies to gluten fraction B present in the sera of two patients with untreated coeliac disease.

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Antiplatelet Effect of Hsien-Ho-T'sao (Agrimonia Pilosa)

The American Journal of Chinese Medicine ◽

10.1142/s0192415x85000150 ◽

1985 ◽

Vol 13 (01n04) ◽

pp. 109-118 ◽

Cited By ~ 7

Author(s):

Jih-Pyang Wang ◽

Mei-Feng Hsu ◽

Che-Ming Teng

Keyword(s):

Platelet Rich Plasma ◽

Atp Release ◽

Water Extract ◽

Creatine Phosphate ◽

Inhibitory Effect ◽

Malondialdehyde Formation ◽

Dependent Inhibition ◽

Dose Dependent Inhibition ◽

Induced Aggregation ◽

Dose Dependent

The water extract of Hsien-Ho-T'sao (HHT) produced a dose-dependent inhibition on collagen-induced aggregation of platelet-rich plasma (PRP). The IC50 was about 3.5 mg/ml. In addition, HHT inhibited also the aggregation induced by ADP, A23187 or arachidonate in PRP. Greater inhibition was observed in the preparation of washed platelets. Increase of the calcium concentration in medium could not overcome the inhibitory effect of HHT. ATP release from platelets induced by collagen or A23187 was inhibited by HHT. In the presence of EDTA, ATP release caused by thrombin or A23187 was also inhibited by HHT. Malondialdehyde and thromboxane B2 formation was greatly inhibited by HHT in platelets challenged by collagen and thrombin. In arachidonate-stimulated platelets, thromboxane B2, but not malondialdehyde formation was inhibited. HHT showed more marked inhibition on aggregation in the presence of indomethacin, creatine phosphate/creatine phosphokinase or a combination of both. Hydrogen peroxide-induced hemolysis was makred reduced by HHT. It was concluded that HHT might have some membrane-active properties which interfered with the activation of phospholipase A2.

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