Analysis of the dose-response relationship of histamine and Nτ-methylhistamine

Stanovnik, Lovro; Erjavec, F.

doi:10.1007/bf01965132

Cited by 5 publications

(1 citation statement)

References 9 publications

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“…Nevertheless, E/[A] curves indistinguishable from hyperbolae are common and cover a wide range of horm one-receptor interactions; for example, (3-adrenoceptor agonists (Ishii et al 1982;Amidon & Buckner 1981); a-adrenoceptor agonists (Fuder 1981;K enakin 1981); serotonergic agonists (Van Neuten al. 1980;Brazenor & Angus 1981) ; histaminergic (H x) agonists (Kenakin & Cook 1980); histaminergic (H2) agonists (Bertaccini & Coruzzi 1981;Stanovnik & Erjavec 1982); muscarinic agonists (Clark 1926); nicotinic agonists (Dean & Downie 1978); opiates (Kamikawa & Shimo 1978); peptides (Regoli 1979;Regoli et al 1974); steroids (Seelig & Sayers 1973); prostaglandins (Asano et al 1982).…”

Section: A General Operational Model Of Agonist Actionmentioning

confidence: 99%

Operational models of pharmacological agonism

1983

Proc. R. Soc. Lond. B.

949

508

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The traditional receptor-stimulus model of agonism began with a description of drug action based on the law of mass action and has developed by a series of modifications, each accounting for new experimental evidence. By contrast, in this paper an approach to modelling agonism is taken that begins with the observation that experimental agonist-concentration effect, E /[A], curves are commonly hyperbolic and develops using the deduction that the relation between occupancy and effect must be hyperbolic if the law of mass action applies at the agonist-receptor level. The result is a general model that explicity describes agonism by three parameters: an agonist-receptor dissociation constant, K A ; the total receptor concentration, [R 0 ]; and a parameter, K E , defining the transduction of agonist-receptor complex, AR, into pharmacological effect. The ratio, [R 0 ]/ K E , described here as the ‘transducer ratio’, τ , is a logical definition for the efficacy of an agonist in a system. The model may be extended to account for non-hyperbolic E /[A] curves with no loss of meaning. Analysis shows that an explicit formulation of the traditional receptor-stimulus model is one particular form of the general model but that it is not the simplest. An alternative model is proposed, representing the cognitive and transducer functions of a receptor, that describes agonist action with one fewer parameter than the traditional model. In addition, this model provides a chemical definition of intrinsic efficacy making this parameter experimentally accessible in principle. The alternative models are compared and contrasted with regard to their practical and conceptual utilities in experimental pharmacology.

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Section: A General Operational Model Of Agonist Actionmentioning

confidence: 99%

Operational models of pharmacological agonism

1983

Proc. R. Soc. Lond. B.

949

508

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Specific binding of [3H]mepyramine to histamine H1-receptors in vascular smooth muscle membranes

Carman-Krzan

1983

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The antagonist-sensitive binding of [3H]mepyramine to beef aortic membranes was as expected for binding to histamine H1-receptors. [3H]mepyramine binds rapidly and in saturable fashion to the specific receptor sites, specific binding reaching equilibrium in 3 min at 37 degrees C. SCATCHARD's analysis of the binding data gave a dissociation constant of 3.0 nM for the radioligand-receptor complex and maximal number of binding sites: 31 fmol/mg protein. In the competition studies histamine H1-antagonists are more potent inhibitors of radioligand binding than H2-antagonist. They inhibit [3H]mepyramine binding in the following order: mepyramine greater than triprolidine greater than promethazine much greater than cimetidine. Binding data are in correlation with the previous pharmacological studies.

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