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Abstract

Differential attenuation of the responses to adenosine and methoxamine in isolated rabbit aorta.

H L Wiener and G P Thalody
Journal of Pharmacology and Experimental Therapeutics November 1993, 267 (2) 828-837;
H L Wiener
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G P Thalody
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Abstract

This article describes the functional antagonism between the responses to adenosine (through adenosine A2 receptors) and methoxamine (through alpha-1 adrenoceptors) in the adventitia- and endothelium-denuded isolated rabbit thoracic aorta. Rings were contracted with different concentrations of methoxamine and cumulative relaxation concentration-response curves (CRC) to adenosine were constructed. This protocol allowed the authors to rearrange the same data, which yielded contractile CRCs to methoxamine in the presence of adenosine. A 32-fold increase in the [methoxamine] markedly attenuated the maximal response to adenosine (80% decrease) and shifted the CRC to adenosine 10-fold to the right. By contrast, a 3000-fold increase in the [adenosine] shifted the CRC to methoxamine 3.25-fold to the right and attenuated the maximal response by a modest 18%. Analysis of these data by the operational model of agonism indicated that the efficacy parameter, tau, for adenosine or methoxamine was reduced by 99% or 71%, respectively, under these conditions. The agonist dissociation constant, KA, for adenosine (80 microM) or methoxamine (33 microM) by functional antagonism was also estimated. Use of an irreversible alpha-1 adrenoceptor antagonist allowed for the estimation of the KA for methoxamine by the receptor inactivation method using the operational model (40 microM), the Furchgott equation (48 microM) and the nested equations (42 microM) described by James et al. These results suggest that this tissue preparation is a good model to study functional antagonism quantitatively and that the functional antagonism between the responses mediated by these two receptors allows for the reliable estimation of the agonist dissociation constant for alpha-1 adrenoceptor agonists.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 267, Issue 2
1 Nov 1993
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Abstract

Differential attenuation of the responses to adenosine and methoxamine in isolated rabbit aorta.

H L Wiener and G P Thalody
Journal of Pharmacology and Experimental Therapeutics November 1, 1993, 267 (2) 828-837;

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Abstract

Differential attenuation of the responses to adenosine and methoxamine in isolated rabbit aorta.

H L Wiener and G P Thalody
Journal of Pharmacology and Experimental Therapeutics November 1, 1993, 267 (2) 828-837;
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