Abstract
1. 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).(ABSTRACT TRUNCATED AT 250 WORDS)
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Selected References
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- ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Adams H. R. Direct myocardial depressant effects of gentamicin. Eur J Pharmacol. 1975 Feb;30(2):272–279. doi: 10.1016/0014-2999(75)90110-7. [DOI] [PubMed] [Google Scholar]
- Adams H. R., Durrett L. R. Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs. J Clin Invest. 1978 Aug;62(2):241–247. doi: 10.1172/JCI109122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BRAZIL O. V., CORRADO A. P. The curariform action of streptomycin. J Pharmacol Exp Ther. 1957 Aug;120(4):452–459. [PubMed] [Google Scholar]
- CORRADO A. P. Respiratory depression due to antibiotics: calcium in treatment. Anesth Analg. 1963 Jan-Feb;42:1–5. [PubMed] [Google Scholar]
- Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
- Hess P., Lansman J. B., Tsien R. W. Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature. 1984 Oct 11;311(5986):538–544. doi: 10.1038/311538a0. [DOI] [PubMed] [Google Scholar]
- Hino N., Ochi R., Yanagisawa T. Inhibition of the slow inward current and the time-dependent outward current of mammalian ventricular muscle by gentamicin. Pflugers Arch. 1982 Sep;394(3):243–249. doi: 10.1007/BF00589099. [DOI] [PubMed] [Google Scholar]
- Ishii K., Taira N., Yanagisawa T. Differential antagonism by Bay k 8644, a dihydropyridine calcium agonist, of the negative inotropic effects of nifedipine, verapamil, diltiazem and manganese ions in canine ventricular muscle. Br J Pharmacol. 1985 Feb;84(2):577–584. doi: 10.1111/j.1476-5381.1985.tb12943.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parker R. B., Waud D. R. Pharmacological estimation of drug-receptor dissociation constants. Statistical evaluation. I. Agonists. J Pharmacol Exp Ther. 1971 Apr;177(1):1–12. [PubMed] [Google Scholar]
- Pittinger C., Adamson R. Antibiotic blockade of neuromuscular function. Annu Rev Pharmacol. 1972;12:169–184. doi: 10.1146/annurev.pa.12.040172.001125. [DOI] [PubMed] [Google Scholar]
- Reuter H. Calcium channel modulation by neurotransmitters, enzymes and drugs. Nature. 1983 Feb 17;301(5901):569–574. doi: 10.1038/301569a0. [DOI] [PubMed] [Google Scholar]
- SWAIN H. H., KIPLINGER G. F., BRODY T. M. Actions of certain antibiotics on the isolated dog heart. J Pharmacol Exp Ther. 1956 Jun;117(2):151–159. [PubMed] [Google Scholar]
- Vital Brazil O., Prado-Franceschi J. The nature of neuromuscular block produced by neomycin and gentamicin. Arch Int Pharmacodyn Ther. 1969 May;179(1):78–85. [PubMed] [Google Scholar]
