EFFECT OF GLUCOCORTICOSTEROID TREATMENT ON BETA-ADRENOCEPTOR SUBTYPE FUNCTION IN ADIPOCYTES FROM PATIENTS WITH ASTHMA

1. Adrenoceptor subtype function was studied in isolated adipocytes ob tained by subcutaneous fat biopsies from nine patients with mild asthm a. The biopsies were taken before and after 7 days treatment with 25 m g of prednisolone given orally. Lipolytic activity after stimulation w ith various adrenergic agents was measured, using glycerol release as an index of lipolysis. The number of beta1- and beta2-adrenoceptor bin ding sites was determined in radioligand binding experiments and beta1 - and beta2-adrenoceptor mRNA levels were measured with a solution hyb ridization assay. 2. Lipolytic sensitivity (ED50) to isoprenaline, a n onselective beta-adrenoceptor agonist, increased 50-fold after treatme nt (P=0.04). Sensitivity to terbutaline, a selective beta2-adrenocepto r agonist, increased 25-fold (P=0.01), whereas the ED50 values for dob utamine, a selective beta1-adrenoceptor agonist, did not change signif icantly. Likewise, the sensitivity to the alpha2-adrenoceptor agonist, clonidine, and to the drugs acting at post-receptor levels did not ch ange significantly. Basal and maximum lipolytic rates on stimulation w ere not altered by the treatment. 3. The number of beta2-adrenoceptor binding sites increased by 60% after treatment (P<0.05), whereas the b eta1-adrenoceptor binding sites were not affected. The affinity of eac h receptor subtype for the displacing ligand, ICI 118.551, was not sig nificantly altered by steroids. No significant changes were demonstrat ed in either beta1- or beta2-adrenoceptor mRNA levels. 4. Thus, glucoc orticoids selectively increase beta2-adrenoceptor density and function in patients with asthma, studied by using subcutaneous fat cells as a n experimental model.