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Relationship between β‐adrenoceptors and calcium channels in human ventricular myocardium
Author(s) -
Ferry D.R.,
Kaumann A.J.
Publication year - 1987
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.1476-5381.1987.tb11194.x
Subject(s) - iodocyanopindolol , dihydroalprenolol , dissociation constant , sarcolemma , prazosin , medicine , calcium , chemistry , endocrinology , cardiology , antagonist , myocyte , intrinsic activity , receptor , partial agonist , agonist
1 The stoichiometric relationship between adrenoceptors and saturable binding sites for 1,4‐dihydropyridines in calcium channels was investigated in human ventricular myocardium. Membrane particles were prepared from heart specimens of patients undergoing open heart surgery. The patients suffered from hypertrophic obstructive cardiomyopathy (HOCM) or mitral valve disease. 2 Using [ 3 H]‐prazosin and [ 125 I]‐2‐β‐hydroxy‐3‐iodiphenyl‐ethyl‐aminoethyl tetralone ([ 125 I]‐HEAT) as labels we detected only a marginal density of α 1 ‐adrenoceptors, regardless of disease. No α 2 ‐adrenoceptors were detected with [ 3 H]‐rauwolscine. 3 In HOCM patients we estimated 72 ± 10 fmol mg −1 ( n = 12) β‐adrenoceptors labelled with [ 3 H]‐(‐)‐dihydroalprenolol and 74 ± 5 fmol mg −1 ( n = 2) β‐adrenoceptors labelled with [ 125 I]‐(‐)‐iodocyanopindolol; the equilibrium dissociation constants K D , were 1.2 ± 0.2 nmol l −1 for [ 3 H]‐(‐)‐dihydroalprenolol and 7 ± 1 pmol l −1 for [ 125 I]‐(‐)‐iodocyanopindolol. In patients with mitral valve disease we estimated 84 ± 11 fmol mg −1 ( n = 3) labelled with [ 3 H]‐(‐)‐dihydroalprenolol and 66 ± 13 fmol mg −1 ( n = 2) labelled with [ 125 I]‐(‐)‐iodocyanopindolol. The K D values were 1.8 ± 0.6 nmol l −1 for [ 3 H]‐(‐)‐dihydroalprenolol and 8 ± 2 pmol l −1 for [ 125 I]‐(‐)‐iodocyanopindolol. 4 In 14 HOCM patients we estimated 107 ± 12 fmol mg −1 calcium channel sites labelled with [ 3 H]‐nimodipine with a K D of 280 ± 4 pmol l −1 . In 5 patients with mitral valve disease the density of calcium channel sites labelled with [ 3 H]‐nimodipine was 78 ± 5 fmol mg −1 with a K D of 290 ± 20 pmol l −1 , In HOCM patients the density of calcium channel sites labelled with the benzoxadiazol 1, 4‐dihydropyridine ([ 3 H]‐(+)‐PN 200–110) was 1.6 fold of that labelled with [ 3 H]‐nimodipine with a K D of 84 ± 11 pmol l −1 . 5 In a group of 4 HOCM patients in which calcium channels were labelled with [ 125 I]‐iodipine, the density of sites was 1.37 ± 0.07 fold the density of sites labelled by [ 3 H]‐(+)‐PN 200‐11‐. The K D value of [ 125 I]‐iodipine was 246 ± 16 pmol −1 . (+)‐PN 200‐110 was approximately 100 fold more potent than (‐)‐PN 200‐110 as a competitor of [ 125 I]‐iodipine binding. 6 For the HOCM group a significant correlation was found between β‐adrenoceptor density and calcium channel density, whereas in the mitral valve group no such correlation was found. This does not prove that there is causal interaction leading to a relationship between the density of β‐adrenoceptors and calcium channels. However, because positive inotropic effects of catecholamines mediated by β‐adrenoceptors are associated with opening of calcium channels, this suggests that the density of both β‐adrenoceptors and calcium channels could be co‐regulated.