Some Quantitative Uses of Drug Antagonists

Arunlakshana, O; Schild, H. O.

doi:10.1111/j.1476-5381.1959.tb00928.x

Cited by 3,036 publications

(1,094 citation statements)

References 21 publications

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“…The extent of aggregation was plotted as a function of the dose of U46619, and these dose-response curves were constructed in the absence and presence of various doses of EPA or DHA. These data were transformed by the method of Arunlakshana and Schild [11]. This analysis revealed slopes not significantly different from one suggesting that DHA and EPA are competitive inhibitors of U46619-induced aggregation at the level of the thromboxane receptor ( fig.2).…”

Section: Resultsmentioning

confidence: 99%

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets

1989

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The present study investigated the mechanism by which eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) inhibit platelet activation induced by thromboxane ,%. DHA was found to be more potent than EPA in blocking platelet aggregation induced by the stable thromboxane A z mimetic, U46619. Furthermore, this inhibition by DHA or EPA was competitive. Binding studies using 3H-U46619 demonstrated that both EPA and DHA interact with the platelet thromboxane receptor. The potency of the inhibition of binding corresponded with that seen for the inhibition of aggregation. These results suggest that thromboxane receptor antagonism may be an important mechanism by which EPA and DHA modulate platelet reactivity in vivo.

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Section: Resultsmentioning

confidence: 99%

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets

1989

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“…The results shown in figs 4 and 5 clearly indicate that analog III is a specific antagonist of (Y-ANP. The Schild analysis [12] of these data has revealed that the inhibitory profile of analog III is competitive and its pA2 value is 7.45 ( fig.6). Thus, it has become clear that analog III binds to the guanylate cyclase-coupled ANP receptor but fails to stimulate the enzyme, probably because of the lack of dimer-to-monomer conversion at the receptor site.…”

Section: Discussionmentioning

confidence: 99%

“…From these results the EDSO values of cy-ANP were estimated as 3.9 x lo-* M in the absence of analog III and 1.4 x 10e7, 4.5 x 10m7, 8.9 x 10e7 and 3.5 x 10e6 M in the presence of 1 x 10-7, 3 x 10m7, 1 x 10T6 and 3 x 10T6 M analog III, respectively. The Schild plots [12] of these data are shown in fig.6, in which the [ED50/(ED& -l] values are plotted vs concentration of analog III on a logarithmic scale, where (EDso) denotes an EDso in the absence of analog III. There exists a good correlation giving an equation of y = 0.99x + 7.3 and a correlation coefficient r = 0.99.…”

Section: Competitive Binding To Vsmcmentioning

confidence: 99%

A dicarba analog of β‐atrial natriuretic peptide (β‐ANP) inhibits guanosine 3′,5′‐cyclic monophosphate production induced by α‐ANP in cultured rat vascular smooth muscle cells

et al. 1989

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The synthesis and biological properties are described of [As~'~~']-/l-ANP-(7-28) (Asu, L-a-aminosuberic acid), a dicarba analog of p-atria1 natriuretic peptide (8-ANP, an antiparallel dimer of human a-ANP with the chains linked by 7-23' and 7-23 disulfide bonds). This Asu-analog (referred to as analog III) displaced 12SI-a-ANP specifically bound to cultured rat vascular smooth muscle cells (VSMC) with an apparent Ki of 2.1 x 10-s M, but did not stimulate formation of intracellular cGMP at 10-8-10-5 M. Analog III inhibited the a-ANP-stimulated cGMP production in VSMC competitively with a pA, value of 7.45 and behaved as an antagonist of a-ANP in rat aorta smooth muscle relaxation. In addition, /I-ANP was also shown to inhibit the a-ANP-induced cGMP production in a dose-dependent manner. The mechanism of action of /I-ANP is also discussed.Atria1 natriuretic peptide analog; Atria1 natriuretic peptide receptor antagonist; Receptor binding; cyclic GMP production; Vasorelaxation; (Cultured vascular smoothmuscle cell)

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“…The kink between heptanol and octanol, however, has not been observed elsewhere. way to measure such effects is by diminution of the maximal contraction (Arunlakshana and Schild, 1959). In practice this was made difficult by the fact that, in the presence of depressants, the maximal contraction tends to diminish with successive doses of stimulant, as shown in Fig.…”

Section: Paramecium Immobilizationmentioning

confidence: 99%

Unspecific Drug Action. The Effects of a Homologous Series of Primary Alcohols

Rang

1960

British Journal of Pharmacology and Chemotherapy

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Experimental results relating to the unspecific depressant action of normal primary alcohols from methanol to octanol on four separate biological systems are presented. It was found that the log‐concentration action curves of alcohols on all four systems were straight over most of their range and, for any one system, parallel throughout the series. With arithmetic increase in the alcohol chainlength the concentration required to produce a given effect diminished logarithmically. The rate of this decrease varied in different biological systems, and was always less than the rate of decrease of solubility with chainlength. In two of the systems investigated alcohols beyond octanol failed to show any activity (cut‐off phenomenon). The implications of these findings are discussed, with reference to the mechanism of action of unspecific depressants. Ferguson's principle of using thermodynamic activity instead of concentration as an index of activity was applied to the present results. In an appendix, the results are compared with predictions according to Mullins' hypothesis of narcotic action, and found not to agree well.

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Some Quantitative Uses of Drug Antagonists

Cited by 3,036 publications

References 21 publications

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets

A dicarba analog of β‐atrial natriuretic peptide (β‐ANP) inhibits guanosine 3′,5′‐cyclic monophosphate production induced by α‐ANP in cultured rat vascular smooth muscle cells

Unspecific Drug Action. The Effects of a Homologous Series of Primary Alcohols

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Some Quantitative Uses of Drug Antagonists

Cited by 3,036 publications

References 21 publications

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A2/prostaglandin H2 receptor in human platelets

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A2/prostaglandin H2 receptor in human platelets

A dicarba analog of β‐atrial natriuretic peptide (β‐ANP) inhibits guanosine 3′,5′‐cyclic monophosphate production induced by α‐ANP in cultured rat vascular smooth muscle cells

Unspecific Drug Action. The Effects of a Homologous Series of Primary Alcohols

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Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets

Eicosapentaenoic acid and docosahexaenoic acid are antagonists at the thromboxane A₂/prostaglandin H₂ receptor in human platelets