Impairment of the beta-adrenergic system of peripheral-blood leukocytes in atopic patients with seasonal allergic rhinoconjunctivitis

Abstract

Compared to 7 healthy women, an altered beta2-adrenoceptor/cyclic adenosine monophosphate (cAMP) system has been observed in a combined study on both expression and function of beta2-adrenoceptors on peripheral blood leukocytes (PBL) of 7 atopic women suffering from acute seasonal rhinoconjunctivitis. A reduced affinity of the beta-adrenergic radioligand I-125 cyanopindolol to its binding site (equilibrium dissociation constant K(d) 6.4+/- 1.0 vs. 3.4 +/-0.6 pmol/l in controls; p < 0.05), a reduced sensitivity of the intracellular cAMP formation to isoprenaline (concentration necessary to achieve half-maximal effectiveness EC50 1,088.6 +/- 669.0 vs. 71.0 +/- 51.0 nmol/l in controls; p<0.01), and a reduced intracellular cAMP increase in response to isoprenaline (E(max) as a percentage of the basal cAMP content E0 117 +/- 3 vs. 145 +/- 8% E0 in controls; p<0.01) point to a subsensitivity of beta2-adrenoceptors. A reduced E0 (4.9 +/- 0.8 vs. 8.4 +/- 1.3 pmol/10(6) cells in controls; p< 0.05) suggests an increased activity of the cAMP-degrading enzyme phosphodiesterase. A reduced sympathetic tone in atopy was further confirmed by lower cAMP plasma concentrations (25.7 +/- 1.2 vs. 31.3 +/- 1.6 nmol/l in controls; p<0.05). The results indicate that more than just one mechanism are involved in the impairment of the PBL beta2-adrenoceptor/cAMP system in atopy.