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DISSOCIATION CONSTANTS OF ISOPRENALINE AND ORCIPRENALINE AND THEIR RELATIVE EFFICACIES ON GUINEA‐PIG ISOLATED ATRIA DETERMINED BY USE OF AN IRREVERSIBLE β‐ADRENOCEPTOR ANTAGONIST
Author(s) -
BROADLEY KENNETH J.,
NICHOLSON C. DAVID
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb09143.x
Subject(s) - orciprenaline , isoprenaline , chronotropic , chemistry , agonist , dissociation constant , antagonist , partial agonist , medicine , endocrinology , receptor , heart rate , biochemistry , stimulation , blood pressure
1 Dissociation constants ( K a ) of isoprenaline and orciprenaline were determined for the positive inotropic and chronotropic responses of guinea‐pig isolated atria. Cumulative dose‐response curves to the agonists were constructed before and after incubation with and washout of the irreversible β‐adrenoceptor antagonist, Ro 03–7894 1‐(5‐chloracetylaminobenzfuran‐2‐yl)‐2‐isopropylaminoethanol). 2 After 20 min washout, the curves were displaced to the right with depression of the maxima. After 3 h washout, there was only depression of the maxima. 3 Dissociation constants were determined by plotting reciprocals of molar concentrations before Ro 03–7894 (1/A) against reciprocals of the equiactive concentrations after Ro 03–7894 (1/A'). K a = (slope‐1)/intercept. 4 Isoprenaline had a greater affinity ( K a ) than orciprenaline on both rate and tension. The affinity for rate and tension was identical for both agonists, indicating that the β‐adrenoceptors were identical. 5 Isoprenaline and orciprenaline produced identical rate response maxima when compared in the same preparation but the orciprenaline tension maximum was only 92.0 ± 0.3% that of isoprenaline. 6 These dose‐response curves were replotted as response against ‐log RA/Rt (fraction of receptors occupied) for each agonist concentration, calculated from the equation RA/Rt = (A)/( K a + (A)). The antilogarithm of the distance along the ‐log RA/Rt axis gave the efficacy of orciprenaline relative to isoprenaline. It had a greater efficacy (2.24) for rate responses but a lower efficacy for tension responses (0.5).