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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
    ISSN: 1432-1912
    Keywords: Chemical sympathectomy ; Inotropic catecholamine effect ; Myocardial adrenoceptors ; Blockade of extraneuronal uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The positive inotropic effects of (−)-noradrenaline and (±)-isoprenaline were studied on guinea-pig papillary muscles after chemical sympathectomy with 6-hydroxydopamine. 1. Pretreatment with 6-hydroxydopamine increased the sensitivity of the papillary muscle to (−)-noradrenaline from a normal EC50 of about 2×10−6 mol/l to 1.5×10−8 mol/l (−)-noradrenaline. The sensitivity to (±)-isoprenaline was not significantly altered. 2. The positive inotropic effect of (−)-noradrenaline was antagonized by (±)-propranolol (10−7, 3×10−6 mol/l) and (±)-practolol (7×10−5 mol/l) with a decrease in slope. In the presence of hydrocortisone (10−4 mol/l), phenoxybenzamine (5×10−6 mol/l) or phentolamine (10−7, 3×10−6 mol/l) (±)-propranolol caused a nearly parallel shift of the concentration-effect curves to the right. Inhibition of monoamine oxidase by pargyline (10−5 mol/l) and of catechol-O-methyl-transferase (COMT) by U-0521 (10−5 mol/l) did not interfere with the (−)-noradrenaline—(±)-propranolol antagonism. 3. The positive inotropic effect of (±)-isoprenaline was antagonized by (±)-propranolol (10−7, 3×10−6 mol/l) with only a slight decrease in slone of the concentration-effect curves. When phentolamine (3×10−6 mol/l) was added to (±)-propranolol, there was no significant further effect. Inhibition of COMT by U-0521 (10−5 mol/l) was without influence on the (±)-isoprenaline—(±)-propranolol antagonism. 4. The results suggest the existence of differences in the mechanism of the positive inotropic effects of (−)-noradrenaline and (±)-isoprenaline at postsynaptic sites. Compartmentalization of two types of adrenoceptors, differing in their affinity to (−)-noradrenaline and (±)-isoprenaline, offers the most probable explanation.
    Type of Medium: Electronic Resource
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