Human lymphocyte and myocardial beta-adrenoceptors: up and down regulation.
Radioreceptor assays have extended the knowledge of beta-adrenoceptor regulation. To evaluate the usefulness of this method in cardiovascular pharmacology, this study was designed to determine: (1) the correlation between beta-adrenoceptor density in human lymphocytes and myocardial cell membranes. This was achieved by using simultaneously harvested left auricles and whole blood samples in 10 patients scheduled to undergo cardiothoracic surgery. The correlation was found to be linear (r = 0.65; P less than 0.05; N = 10); (2) the changes in lymphocyte receptor density and affinity in heart failure. Lymphocytes were harvested from 6 healthy volunteers, 8 patients with moderate heart failure (NYHA class I or II) and 8 patients with severe heart failure (NYHA class III or IV). Mean densities observed were 75.6 +/- 11, 46.3 +/- 18 and 26.4 +/- 5.9 fmol/mg protein, respectively, and dissociation constants were 62.8 +/- 16; 67.8 +/- 14, and 46 +/- 26 pM. The number of receptors fell significantly from one heart failure class to that immediately above it (P less than 0.01; N = 22); (3) the beta-adrenoceptor regulatory properties of a class I antiarrhythmic drug, propafenone, the chemical structure of which is similar to that of the beta-blocking drug propranolol. Five patients needing antiarrhythmic treatment were given 10 d of oral propafenone treatment (450-900 mg/day). Mean adrenoceptor densities (Bmax) were 22.7 +/- 9 and 43.7 +/- 9 fmol/mg protein, and dissociation constants (KD) values were 24.7 +/- 20 and 27 +/- 18 pM respectively, before and after 10 d of chronic treatment. The number of receptors increased significantly after 10 d of treatment (P less than 0.01; N = 5).(ABSTRACT TRUNCATED AT 250 WORDS)
Sbirrazzuoli
V
V
Département de Pharmacologie Clinique, Faculté de Médecine, Nice, France.
Lapalus
P
P
D015536:Down-Regulation; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011405:Propafenone / Q000627:therapeutic use; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
D011943:Receptors, Adrenergic, beta; D011405:Propafenone