Beta-adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children.

Abstract

Beta-adrenoceptor binding in lymphocytes of asthmatic and non-asthmatic children and healthy adult volunteers was investigated with the radioligand 125-iodocyanopindolol (ICYP). Binding studies were performed with 4 to 5 different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of beta-adrenoceptors into those of high and low affinity state was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density in B-cell enriched fractions was two to three-fold higher than in T-cells for all patients and volunteers studied (P less than 0.025). No difference in beta-adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of beta-adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for beta-adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that beta-adrenoceptors on T-cells were at a higher affinity state compared to those on B-cells in asthmatic and non-asthmatic children, as well as in adults. Since the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity receptor state formed in the presence of the agonist, increased intrinsic activity of the beta-adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are necessary for interpretation of beta-adrenoceptor changes in bronchial asthma.