PHARMACOLOGICAL APPROACHES TO THE CHARACTERIZATION OF β-ADRENORECEPTOR POPULATIONS IN TISSUES

• 1 The locations of the Schild plots for a selective β-adrenoreceptor antagonist using different agonists have been used as a means of determining whether the β-adrenoreceptor population of a tissue is heterogeneous (β₁ plus β₂) or homogeneous (β₁ or β₂).
• 2 On guinea-pig trachea, Schild plots for ICI 118,551 (β₂-selective adrenoreceptor antagonist), obtained using fenoterol (β₂-selective) or noradrenaline (β₁-selective) as agonist, were separated, indicating a heterogeneous β-adrenoreceptor population. In contrast, Schild plots for a non-selective antagonist, pindolol, using the same two agonists, were superimposed.
• 3 On guinea-pig trachea, the Schild plot for ICI 118,551 with salbutamol (β₂-selective agonist) was superimposed on that with fenoterol (slopes of both plots were close to unity). The Schild plots for ICI 118,551 with adrenaline or rimiterol (β₂-selective agonists) gave pA₂ values similar to those obtained with fenoterol or salbutamol as agonist, although the slopes of these plots were less than unity. The Schild plot obtained using any of these β₂-selective agonists was clearly separated from that using noradrenaline. This was in contrast to guinea-pig atria where Schild plots were superimposed whatever the β-adrenoreceptor agonist used.
• 4 These data confirmed that, in a tissue with a heterogeneous β-adrenoreceptor population, separated Schild plots for an antagonist are obtained only if the antagonist is selective and if agonists of differing selectivity are used. This is the theoretically predictable result.
• 5 Data were also obtained (for the positive chronotropic response of guinea-pig, rat and cat atria and for the relaxation response of guinea-pig trachea) using another method for determining whether or not the β-adrenoreceptor population of a tissue is homogeneous. This method did not require the use of selective agonists.
• 6 The concentration ratios obtained for the antagonism of isoprenaline by atenolol (β₁-selective) and ICI 118,551 alone and then in combination, indicated the involvement of a single β-adrenoreceptor population in responses of guinea-pig and rat atria but not of cat atria and guinea-pig trachea. These results were consistent with conclusions from Schild plot experiments that positive chronotropic responses in rat and guinea-pig atria involve only β₁-adrenoreceptors whereas chronotropic responses in cat atria and relaxation of guinea-pig trachea involve both β₁ and β₂-adrenoreceptors.