Relations between β-adrenoceptor occupancy and increases of contractile force and adenylate cyclase activity induced by catecholamines in human ventricular myocardium: acute desensitization and comparison with feline ventricle

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1989, Vol.339 (1-2), p.99-112
• Main Authors: KAUMANN, A. J, LEMOINE, H, SCHWEDERSKI-MENKE, U, EHLE, B
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Biological and medical sciences; Catecholamines - pharmacology; Cats; Cell Membrane - drug effects; Cell Membrane - metabolism; Dopamine - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Heart; Heart - drug effects; Humans; In Vitro Techniques; Isoproterenol - antagonists & inhibitors; Middle Aged; Myocardial Contraction - drug effects; Myocardium - enzymology; Myocardium - metabolism; Receptors, Adrenergic, beta - metabolism; ventricle; Vertebrates: cardiovascular system
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00165132

The function of beta-adrenoceptors was investigated in ventricular myocardium obtained from patients undergoing open heart surgery. 1. 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. 2. beta-Adrenoceptors were labelled with 3H-(-)-bupranolol. For 3/4 of the receptors (beta 1) the affinity of (-)-noradrenaline was 20 times higher than for the remaining 1/4 (beta 2). (-)-Adrenaline and dopamine appeared to be non-selective for beta 1 and beta 2. 3. Dopamine was able to stimulate the adenylate cyclase only up to 1/3 of the maximum stimulation caused by (-)-noradrenaline and (-)-adrenaline. 4. Increases in contractile force by (-)-noradrenaline were closely associated with small increases of cyclase activity through beta 1-adrenoceptors, consistent with a common link. 5. 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. 6. A 3 h exposure of human and feline ventricular myocardium to (-)-isoprenaline caused desensitization by uncoupling beta-adrenoceptors from the adenylate cyclase. Desensitization reduced the maximum contractile response to (-)-isoprenaline in human but not in feline ventricle. 7. 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 beta 1-adrenoceptors, a 6-fold higher production of cyclic AMP per beta 1-adrenoceptor and possibly to a more effective use of cyclic AMP for contraction.