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Differential antagonism of the negative inotropic effect of gentamicin by calcium ions, Bay K 8644 and isoprenaline in canine ventricular muscle: comparison with cobalt ions
Author(s) -
Hashimoto Hiroo,
Yanagisawa Teruyuki,
Taira Norio
Publication year - 1989
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.1476-5381.1989.tb11901.x
Subject(s) - isoprenaline , schild regression , inotrope , chemistry , chronotropic , antagonism , calcium , endocrinology , medicine , heart rate , biology , receptor , biochemistry , organic chemistry , stimulation , blood pressure
1 Gentamicin (10 −4 −10 −2 m ) and Co 2+ (10 −4 — 10 −2 m ) produced a decrease in developed tension of canine isolated ventricular muscles leading to near abolition at 10 −2 m . Their negative inotropic effects developed rapidly and wore off shortly after wash‐out. 2 The concentration‐negative inotropic effect curves for gentamicin were shifted to the right in a parallel manner by increasing external Ca 2+ , or by the presence of Bay K 8644 (10 −7 −10 −5 m ) or isoprenaline (10 −7 −10 −5 m ). IC 50 values for gentamicin increased about 3‐fold with about a 6 fold increase in external Ca 2+ . The Schild plot yielded a pA 2 of 2.29 for Ca 2+ and its slope was −1.17 ( r = −0.79). 3 The concentration‐negative inotropic effect curves for Co 2+ were shifted to the right in a parallel manner by increasing external Ca 2+ , or by the presence of isoprenaline (10 −7 −10 −5 m ). IC 50 values for Co 2+ increased about 5 fold with about a 6 fold increase in external Ca 2+ . The Schild plot gave a pA 2 value of 2.60 for Ca 2+ and its slope was −1.11 ( r = −0.86). 4 The concentration‐positive inotropic effect curves for Ca 2+ , which were computer‐fitted to a logistic equation, gave 2.88 × 10 −3 m for EC 50 . This value was very close to the K Ca calculated from pA 2 values for Ca 2+ based on antagonism between gentamicin or Co 2+ and Ca 2+ (5.13 × 10 −3 and 2.51 × 10 −3 m ). 5 It is concluded that like Co 2+ , gentamicin molecules compete with Ca 2+ for the same binding sites presumably located at the outer orifice of Ca‐channels in the cardiac sarcolemma.