Relations between ?-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium

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Abstract
The function of β-adrenoceptors was investigated in ventricular myocardium obtained from patients undergoing open heart surgery. Dopamine increased contractile force up to 1/2 and 1/4 of the maximum increase caused by (−)-noradrenaline or (−)-adrenaline in right and left ventricular preparations, respectively. β-adrenoceptors were labelled with 3H-(−)-bupranolol. For 3/4 of the receptors (β1) the affinity of (−)-noradrenaline was 20 times higher than for the remaining 1/4 (β2). (−)-Adrenaline and dopamine appeared to be nonselective for β1 and β2. Dopamine was able to stimulate the adenylate cyclase only up to 1/3 of the maximum stimulation caused by (−)noradrenaline and (−)-adrenaline. Increases in contractile force by (−)-noradrenaline were closely associated with small increases of cyclase activity through β1-adrenoceptors, consistent with a common link. The experiments on human myocardium were compared with similar experiments on feline myocardium. Feline ventricle exhibited a 20- to 30-fold higher sensitivity to catecholamines as activators of contractile force than did human ventricle. However, the binding affinities for catecholamines were similar in cat and man. A 3 h exposure of human and feline ventricular myocardium to (−)-isoprenaline caused desensitization by uncoupling β-adrenoceptors from the adenylate cyclase. Desensitization reduced the maximum contractile response to (−)-isoprenaline in human but not in feline ventricle. The more efficient activation of contractile force by (−)-noradrenaline in cat, compared to man, appears to be related to a 2-fold higher density of β1-adrenoceptors, a 6-fold higher production of cyclic AMP per β1-adrenoceptor and possibly to a more effective use of cyclic AMP for contraction.

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