The positive inotropic effect of (?)-noradrenaline and (�)-isoprenaline after chemical sympathectomy: Evidence in favour of differences at a postsynaptic site

Ebner, F.; Fleig, H. A.; Trendelenburg, U.

doi:10.1007/bf00507220

Cited by 18 publications

(1 citation statement)

References 26 publications

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“…Tissues were allowed to equilibrate for 30 rnin without electrical stimulation and a further 60 rnin with stimulation. No inhibitors of extraneuronal uptake of catecholamines were included in the medium since this removal mechanism has been shown not to significantly affect the location of concentration-response curves to isoprenaline in this tissue (Ebner, 1981).…”

Section: Guinea-pig Papillary Musclementioning

confidence: 99%

The Measurement of the Relative Efficacy of Agonists by Selective Potentiation of Tissue Responses: Studies With Isoprenaline and Prenalterol in Cardiac Tissue

Kenakin

Beek

1984

Journal of Autonomic Pharmacology

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Isoprenaline, but not prenalterol, produced positive inotropy in guinea-pig papillary muscle. Prenalterol was a competitive antagonist of responses to isoprenaline in this tissue with a pKB of 7.24, as estimated by a Schild regression. Guinea-pig papillary muscles pretreated with the phosphodiesterase inhibitor, isobutylmethylxanthine (IMX), were 10 times more sensitive than controls to isoprenaline. In these tissues, prenalterol was a partial agonist producing 68% of the maximal response to isoprenaline. Schild regressions with atenolol indicated no change in beta-adrenoreceptors with IMX treatment and also that isoprenaline and prenalterol activated the same receptor in this tissue. The relative efficacy of isoprenaline and prenalterol was measured by using the KB estimated by Schild analysis for prenalterol and a Kd for isoprenaline from published binding studies. The relative efficacy of these drugs (epsilon ISO/epsilon PREN) was 242 +/- 29. The general method of potentiation of responses to weak agonists to estimate relative efficacy is discussed.

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Section: Guinea-pig Papillary Musclementioning

confidence: 99%

The Measurement of the Relative Efficacy of Agonists by Selective Potentiation of Tissue Responses: Studies With Isoprenaline and Prenalterol in Cardiac Tissue

Kenakin

Beek

1984

Journal of Autonomic Pharmacology

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Alpha‐adrenoceptors: A critical review

McGrath

Brown

Wilson

1989

Medicinal Research Reviews

100

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The effects on Schild regressions of antagonist removal from the receptor compartment by a saturable process

Kenakin

Beek

1987

Naunyn-Schmiedeberg's Arch Pharmacol

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A theoretical model of the effects of a saturable removal mechanism for an antagonist diffusing into the receptor compartment of a tissue is used to calculate expected deviations in Schild regressions. At concentrations of antagonist which do not saturate the removal mechanism, there can be a deficit of antagonist in the receptor compartment as compared to the concentration of antagonist bathing the tissue. This results in a shift to the right of the Schild regression and a corresponding underestimation of antagonist potency. The model predicts that as the concentration of antagonist exceeds the Km for removal (saturation of the removal process), this concentration deficit is eliminated, resulting in a proportionate increase in antagonist concentration at the receptor and a concomitant increase in receptor antagonism. This results in a steepening of the Schild regression; the slope in the region of saturation is greater than one. Experimental evidence in support of this model was found in studies of the antagonism of responses to bethanechol by atropine in rabbit ileum; this species is known to have an atropinesterase capable of hydrolyzing atropine. The Schild regression for atropine was curvilinear with an overall slope of 1.42 (1.34-1.5) and pKB = 8.5 (8.36-8.8); in the ileum from guinea pigs, a species which does not possess this enzyme, the Schild regression for atropine was linear, had a slope not significantly different from unity (1.1; 0.95-1.2) and a pKb of 9.0 (8.9-9.2). The slope of the regression in rabbit ileum was corrected to unity by the addition of an excess concentration of methylbutyrate, an alternate substrate for atropinesterase.(ABSTRACT TRUNCATED AT 250 WORDS)

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The positive inotropic effect of (?)-noradrenaline and (�)-isoprenaline after chemical sympathectomy: Evidence in favour of differences at a postsynaptic site

Cited by 18 publications

References 26 publications

The Measurement of the Relative Efficacy of Agonists by Selective Potentiation of Tissue Responses: Studies With Isoprenaline and Prenalterol in Cardiac Tissue

The Measurement of the Relative Efficacy of Agonists by Selective Potentiation of Tissue Responses: Studies With Isoprenaline and Prenalterol in Cardiac Tissue

Alpha‐adrenoceptors: A critical review

The effects on Schild regressions of antagonist removal from the receptor compartment by a saturable process

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