Premium
Contribution of β 1 ‐ and β 2 ‐adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (−)‐atenolol
Author(s) -
Lemoine H.,
Schönell H.,
Kaumann A.J.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb16548.x
Subject(s) - atenolol , inotrope , ventricle , atrium (architecture) , medicine , endocrinology , chemistry , cyclase , catecholamine , stimulation , blood pressure , atrial fibrillation
1 (−)‐Atenolol was used as a tool to assess the function of β 1 and β 2 ‐adrenoceptors in human heart. Right atrial and left ventricular preparations from patients undergoing open heart surgery were set up to contract isometrically. Membrane particles were prepared for β‐adrenoceptor labelling with [ 3 H]‐(−)‐bupranolol and adenylate cyclase assays. 2 The positive inotropic effects of (−)‐noradrenaline were antagonized to a similar extent by (−)‐atenolol in atrial and ventricular preparations. (−)‐Atenolol consistently antagonized the effects of (−)‐adrenaline to a lesser extent than those of (−)‐noradrenaline in atrial preparations. In ventricular preparations (−)‐atenolol antagonized the effects of low concentrations of (−)‐adrenaline to a lesser extent than those of high concentrations. 3 pK B values ( M ) of (−)‐atenolol, estimated with non‐linear analysis from the blockade of the positive inotropic effects of the catecholamines, were 7.4 for β 1 ‐adrenoceptors and 6.0 for β 2 ‐adrenoceptors. 4 (−)−Atenolol inhibited the binding of [ 3 H]‐(−)‐bupranolol to ventricular β 1 ‐adrenoceptors with a pK D ( M ) of 5.9 and to ventricular β 2 ‐adrenoceptors with a pK D of 4.6. 5 (−)‐Atenolol inhibited the catecholamine‐induced adenylate cyclase stimulation in the atrium and ventricle with pK B values of 5.8‐6.4 for β 1 and pK B values of 4.7‐5.7 for β 2 ‐adrenoceptors. The binding and cyclase assays suggest a partial affinity loss for (−)‐atenolol inherent to membrane preparations. 6 β 1 ‐Adrenoceptors mediate the maximum positive inotropic effects of (−)‐noradrenaline in both the atrium and ventricle of man. β 2 ‐Adrenoceptors appear to be capable of mediating maximal positive inotropic effects of (−)‐adrenaline in atrium. In contrast, ventricular β 2 ‐adrenoceptors mediate only submaximal effects of (−)‐adrenaline.