Summary
The positive inotropic effects of catecholamines were studied on samples of ventricular myocardium taken from patients undergoing open heart surgery. The adenylyl cyclase and binding of 3H-(−)-bupranolol were examined in membrane particles prepared from similarly obtained samples.
The equilibrium dissociation constant (K D ) for (−)-bupranolol was estimated in 4 ways: blockade of the positive inotropic effects of catecholamines, blockade of the stimulation of the adenylyl cyclase by catecholamines, saturation binding of 3H-(−)-bupranolol, inhibition of the binding of 3H-(−)-bupranolol by its unlabeled stereoisomers. The estimates of K D fall in the range 0.5–1.4 nmol/l. The stereo-selectivity ratio (K D (+)-isomer/K D (−)-isomer) is 73. Both values for bupranolol are very similar in cat and man.
The inotropic potency of (−)-noradrenaline is nearly 2 orders of magnitude higher in cat heart tissues than in tissues from human hearts. The difference in inotropic potencies between species is only partially accounted for by the five-fold lower potency of (−)-noradrenaline for the human heart adenylyl cyclase as compared to the cat enzyme.
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Kaumann, A.J., Lemoine, H., Morris, T.H. et al. An initial characterization of human heart β-adrenoceptors and their mediation of the positive inotropic effects of catecholamines. Naunyn-Schmiedeberg's Arch. Pharmacol. 319, 216–221 (1982). https://doi.org/10.1007/BF00495868
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DOI: https://doi.org/10.1007/BF00495868