An initial characterization of human heart β-adrenoceptors and their mediation of the positive inotropic effects of catecholamines
AJ Kaumann, H Lemoine, TH Morris… - Naunyn-Schmiedeberg's …, 1982 - Springer
AJ Kaumann, H Lemoine, TH Morris, U Schwederski
Naunyn-Schmiedeberg's Archives of Pharmacology, 1982•SpringerThe 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 3 H-(−)-bupranolol were examined in membrane particles prepared from similarly
obtained samples. The equilibrium dissociation constant (KD) 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 3 H-(−) …
myocardium taken from patients undergoing open heart surgery. The adenylyl cyclase and
binding of 3 H-(−)-bupranolol were examined in membrane particles prepared from similarly
obtained samples. The equilibrium dissociation constant (KD) 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 3 H-(−) …
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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