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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 1-6 
    ISSN: 1432-1912
    Keywords: Cardiac ventricular muscle ; Muscle geometry ; Catecholamine uptake ; Inotropic noradrenaline effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The influence of a saturable drug uptake on the drug concentration near the receptor sites was shown theoretically to depend on the geometry of the preparation; increases in the volume/surface ratio (V/S) of the preparation decrease the sensitivity of the preparation to an agonist inactivated in the tissue. 2. The positive inotropic effect of (-)-noradrenaline was found to depend on the ratio V/S of the preparation; papillary muscles with larger V/S were less sensitive to the drug and showed steeper noradrenaline concentration-effect curves. 3. An algorithm for the statistical estimation of the parameters of the saturable uptake process was derived. It was applied to the positive inotropic noradrenaline effect in relation to muscle geometry. As an analysis of variance showed, the model explained a significant proportion of the shift of (-)-noradrenaline concentration-effect curves associated with variation in size of the preparation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 303 (1978), S. 111-119 
    ISSN: 1432-1912
    Keywords: Magnesium, negative inotropic effect ; Cardiac ventricular muscle ; Mg, Ca, Na antagonism ; Competitive antagonism with two antagonists
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Mg2+, in the investigated range up to 19.2 mM, produced a concentration-dependent reduction of the force of contraction (F c ) of the guinea-pig papillary muscle. Addition of 10 mM Mg2+ to a Mg2+-free bath solution diminished F c to about 50%. 2. The duration of the action potential was slightly prolonged by 19.2 mM Mg2+ (15 ms at 90% repolarization), and the velocity of depolarization was slightly diminished (by 9%). 3. The negative inotropic effect of Mg2+ was primarily the consequence of a decrease in contraction velocity (S 1), i.e., of a negative klinotropic effect. There was a 12% diminution of the time to peak force (t 1) and a 13% prolongation of the relaxation time (t 2) by an elevation of [Mg2+]0 up to 19.2 mM. 4. The curve representing the relation between [Ca2+]0 and contraction velocity (S 1) was shifted to the right by an increase in [Mg2+]0. There was a linear dependence on Mg2+ of the calcium concentrations that were needed to sustain a definite level of S 1 (equieffective [Ca2+]0). A computed regression for this dependence indicates that the negative klinotropic effect of an addition of 10 mM Mg2+ to a solution containing 2.15 mM Ca2+ and no Mg2+ will be antagonized by addition of 0.83 mM Ca2+. 5. These results are compatible with a competitive antagonism between Mg2+ and Ca2+ in regard to their binding to a hypothetical receptor. The apparent dissociation constant of the Mg2+-receptor complex would be about 25 mM in the presence of 140 mM Na+. 6. The negative klinotropic potency of Mg2+ and the positive klinotropic potency of Ca2+ were augmented to a similar degree by a reduction of [Na+]0. 7. The possibility is discussed that Na+ competes with Mg2+ and Ca2+ for a common receptor at the cellular surface. In such a case, for the condition that either 1 Mg2+, 1 Ca2+ or 2 Na+ can be bound by the receptor, the apparent dissociation constant of the Mg2+-receptor complex, as estimated by extrapolation to 0 mM Na+ would be about 6 mM.
    Type of Medium: Electronic Resource
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