J Mol Cell Cardiol 18 (Supplement I) (1986)

12 THE FUNCTION OF ~- AND B-ADRENOCEPTORS IN ISOLATED HEART MUSCLE OF MAN. Alberto J. Kaumann. Dept of Clinical Physiology, University of Dusseldorf, Universitatsstr 1, 4000 Dusseldorf, FRG. Biochemical data from membrane particles of human myocardium are compared with contractile force data. Using 3H-prazosin and 1251-IBE 2254 as markers, only a marginal density of ventricular :l-adrenoceptors (~ 10 fmol. mg -1 protein) was detected, regardless of disease. No :2-adrenoceptors were found using 3H-rauwolscine. These findings are inconsistent with a hypothesis for a major role of ~-adrenoceptors causing the positive inotropic effects of physiological catechamines in human myocardium.

86 fmol. mg-1 and 84 fmol. mg-1 B-adrenoceptors were found in the ventricle of patients with hypertrophic obstructive myopathy (HOCM) and in patients with mitral lesion, respectively. 1251-(-)-cyanopindolol labelled similar densities of 6-adrenoceptors. For the HOCM group but not the mitral group a significant correlation was found between the density of B-adrenoceptors and calcium channel sites (using 3H-nimodipine and 3H-PN 200,110 as markers), suggesting that both 6-adrenoceptors and calcium channels are coregulated.

The fractions of B-adrenoceptor subtypes were 3/4 B1 a~d_l/4 62 in human ventricle which agrees with kitten ventricle (4/5 51, /b62), as estimated with 3H-(-)-bupranolol, as a marker, and competing ligands selective for 61- or 62-adrenoceptors. In the presence of an antagonist that almost exclusively blocks 61-adrenoceptors (selectivity for 61/62 > 1000) (-)-adrenaline can cause increases of contractile force in isolated ventricular tissues amounting up to 50% of maximum increases observed in the absence of blockade of 6-adrenoceptors. Both (-)-propranolol and (-)-pindolol antagonise the positive inotropic effects of (-)-adrenaline more than those of (-)-noradrenaline in atrial tissues, as expected from the antagonist's higher aff ini ty for 62- than for 61-adrenoceptors. These results are consistent with a physiological role of 62-adrenoceptors in causing the positive inotropic effects of (-)-adrenaline in man.

One third only of maximum stimulation of human ventricular and atrial adenylate cyclase by (-)-noradrenaline occurs via 61, 2/3 via 62-adrenor as estimated with the use of antagonists selective for each receptor subtype. Most of the cyclase stimulation by (-)-adrenaline is mediated via 62-adrenoceptors. These results differ considerably from results in kitten ventricle, in which 4/5 of maximum cyclase stimulation by both (-)-noradrena~ine and (-)-adrenaline is mediated by 61-adrenoceptors and only 1/5 by 62-adrenoceptors.