钙离子、Bay K 8644和异丙肾上腺素对庆大霉素在犬心室肌中负性肌力作用的差异性拮抗：与钴离子的比较

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.

作者信息

Hashimoto H, Yanagisawa T, Taira N

机构信息

Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.

出版信息

Br J Pharmacol. 1989 Apr;96(4):906-12. doi: 10.1111/j.1476-5381.1989.tb11901.x.

DOI:10.1111/j.1476-5381.1989.tb11901.x

PMID:2472847

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1854442/

Abstract

Gentamicin (10(-4)-10(-2) M) and Co2+ (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 Ca2+, or by the presence of Bay K 8644 (10(-7)-10(-5) M) or isoprenaline (10(-7)-10(-5) M). IC50 values for gentamicin increased about 3-fold with about a 6 fold increase in external Ca2+. The Schild plot yielded a pA2 of 2.29 for Ca2+ and its slope was -1.17 (r = -0.79). 3. The concentration-negative inotropic effect curves for Co2+ were shifted to the right in a parallel manner by increasing external Ca2+, or by the presence of isoprenaline (10(-7)-10(-5) M). IC50 values for Co2+ increased about 5 fold with about a 6 fold increase in external Ca2+. The Schild plot gave a pA2 value of 2.60 for Ca2+ and its slope was -1.11 (r = -0.86). 4. The concentration-positive inotropic effect curves for Ca2+, which were computer-fitted to a logistic equation, gave 2.88 x 10(-3) M for EC50. This value was very close to the KCa calculated from pA2 values for Ca2+ based on antagonism between gentamicin or Co2+ and Ca2+ (5.13 x 10(-3) and 2.51 x 10(-3) M). 5. It is concluded that like Co2+, gentamicin molecules compete with Ca2+ for the same binding sites presumably located at the outer orifice of Ca-channels in the cardiac sarcolemma.

摘要

庆大霉素（10⁻⁴ - 10⁻² M）和Co²⁺（10⁻⁴ - 10⁻² M）可使犬离体心室肌的舒张张力降低，在10⁻² M时接近完全消失。它们的负性肌力作用发展迅速，冲洗后很快消退。2. 通过增加细胞外Ca²⁺浓度，或加入Bay K 8644（10⁻⁷ - 10⁻⁵ M）或异丙肾上腺素（10⁻⁷ - 10⁻⁵ M），庆大霉素的浓度 - 负性肌力作用曲线平行右移。细胞外Ca²⁺浓度增加约6倍时，庆大霉素的IC50值增加约3倍。Schild图得出Ca²⁺的pA2为2.29，斜率为 -1.17（r = -0.79）。3. 通过增加细胞外Ca²⁺浓度，或加入异丙肾上腺素（10⁻⁷ - 10⁻⁵ M），Co²⁺的浓度 - 负性肌力作用曲线平行右移。细胞外Ca²⁺浓度增加约6倍时，Co²⁺的IC50值增加约5倍。Schild图得出Ca²⁺的pA2值为2.60，斜率为 -1.11（r = -0.86）。4. 经计算机拟合逻辑方程得到的Ca²⁺浓度 - 正性肌力作用曲线，其EC50为2.88×10⁻³ M。该值与根据庆大霉素或Co²⁺与Ca²⁺之间的拮抗作用计算出的Ca²⁺平衡解离常数（KCa）非常接近（分别为5.13×10⁻³ M和2.51×10⁻³ M）。5. 得出结论：与Co²⁺一样，庆大霉素分子与Ca²⁺竞争可能位于心肌肌膜钙通道外口的相同结合位点。