Effect of glucocorticosteroid treatment on beta-adrenoceptor subtype function in adipocytes from patients with asthma.
1. Adrenoceptor subtype function was studied in isolated adipocytes obtained by subcutaneous fat biopsies from nine patients with mild asthma. The biopsies were taken before and after 7 days treatment with 25 mg of prednisolone given orally. Lipolytic activity after stimulation with various adrenergic agent was measured, using glycerol release as an index of lipolysis. The number of beta 1- and beta 2-adrenoceptor binding sites was determined in radioligand binding experiments and beta 1- and beta 2-adrenoceptor mRNA levels were measured with a solution hybridization assay. 2. Lipolytic sensitivity (ED50) to isoprenaline, a non-selective beta-adrenoceptor agonist, increased 50-fold after treatment (P = 0.04). Sensitivity to terbutaline, a selective beta 2-adrenoceptor agonist, increased 25-fold (P = 0.01), whereas the ED50 values for dobutamine, a selective beta 1-adrenoceptor agonist, did not change significantly. Likewise, the sensitivity to the alpha 2-adrenoceptor agonist, clonidine, and to the drugs acting at post-receptor levels did not change significantly. Basal and maximum lipolytic rates on stimulation were not altered by the treatment. 3. The number of beta 2-adrenoceptor binding sites increased by 60% after treatment (P < 0.05), whereas the beta 1-adrenoceptor binding sites were not affected. The affinity of each receptor subtype for the displacing ligand, ICI 118.551, was not significantly altered by steroids. No significant changes were demonstrated in either beta 1- or beta 2-adrenoceptor mRNA levels. 4. Thus, glucocorticoids selectively increase beta 2-adrenoceptor density and function in patients with asthma, studied by using subcutaneous fat cells as an experimental model.
Reynisdottir
S
S
Research Center, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.
Wahrenberg
H
H
Bylin
G
G
Arner
P
P
D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000378:metabolism*; D002478:Cells, Cultured; D003000:Clonidine / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D011239:Prednisolone; D007545:Isoproterenol; D003000:Clonidine; D013726:Terbutaline