An analysis of the alpha- and beta-effects of isoprenaline on the isolated nictitating membrane

Abstract

The effects of isoprenaline were studied on the isolated nictitating membrane. 1. Experiments with specific receptor antagonists and determinations of relative potencies of catecholamines indicated that contractile responses to isoprenaline were mediated by alpha-adrenoceptors and relaxant effects by beta-adrenoceptors. 2. In the absence of any receptor antagonists the alpha-effects of isoprenaline interfere with measurements of the beta-effects (and vice versa). Hence, pD2-values and intrinsic activities determined for the beta-effects of isoprenaline in the absence of phentolamine must be regarded as apparent values. 3. For an agent which potentiates the beta-effects of isoprenaline without affecting its alpha-effects (e.g., hydrocortisone), the apparent degree of super-sensitivity to the beta-effects (determined in the absence of phentolamine) is an underestimate of the true degree of supersensitivity. 4. The magnitude of the relaxant response to a given concentration of isoprenaline was greatest for half-contracted muscles and very small for fully contracted or fully relaxed muscles. The apparent pD2 for the beta-effects of isoprenaline was negatively correlated with the height of steady-state contraction existing prior to the administration of isoprenaline. This correlation was largely independent of the agonist used to elicit the contraction. Hence, the state of the contractile system determines the response to isoprenaline. 5. The relaxant effect of theopyhylline also depended on the state of the contractile system. Theophylline failed to potentiate the beta-effects of isoprenaline. 6. The present results largely verify the validity of earlier measurements of the pD2 for the alpha- and beta-effects of isoprenaline. Experiments with specific receptor antagonists and determinations of relative potencies of catecholamines indicated that contractile responses to isoprenaline were mediated by alpha-adrenoceptors and relaxant effects by beta-adrenoceptors. In the absence of any receptor antagonists the alpha-effects of isoprenaline interfere with measurements of the beta-effects (and vice versa). Hence, pD2-values and intrinsic activities determined for the beta-effects of isoprenaline in the absence of phentolamine must be regarded as apparent values. For an agent which potentiates the beta-effects of isoprenaline without affecting its alpha-effects (e.g., hydrocortisone), the apparent degree of super-sensitivity to the beta-effects (determined in the absence of phentolamine) is an underestimate of the true degree of supersensitivity. The magnitude of the relaxant response to a given concentration of isoprenaline was greatest for half-contracted muscles and very small for fully contracted or fully relaxed muscles. The apparent pD2 for the beta-effects of isoprenaline was negatively correlated with the height of steady-state contraction existing prior to the administration of isoprenaline. This correlation was largely independent of the agonist used to elicit the contraction. Hence, the state of the contractile system determines the response to isoprenaline. The relaxant effect of theopyhylline also depended on the state of the contractile system. Theophylline failed to potentiate the beta-effects of isoprenaline. The present results largely verify the validity of earlier measurements of the pD2 for the alpha- and beta-effects of isoprenaline.

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