Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children

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Abstract
Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined β-adrenoceptor blockade and a hyperresponsiveness of α-andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to β-blockers, a reduced formation of cyclic AMP in response to β-adrenergic stimulation and enhanced α-adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled α-and β-adrenergic antagonists made it possible to study α- and β-adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed α- and β-receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases. Using 125[I]-cyanopindolol (ICYP) and 3[H]-yohimbine (HYOH) as highly specific ligands for α- and β-adrenoceptors, the following results were obtained: (1) Lymphocytes and platelets from control subjects and asthamatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of α- and β-adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. (2) In asthmatic children receiving 4×2 puffs salbutamol β-adrenoceptor were down-regulated and this may mimic β-adrenoceptor blockade. (3) When subjects were divided into four categories according to age (0–5, 5–10, 10–20 years, adults) the number of β-adrenoceptor binding sites showed an age-dependent increase. The number and affinity of α-adreneceptor binding sites on platelets was neither influenced by age nor disease. It is concluded that the α- and β-adrenoceptors of wheezing infants and asthmatic children at least on blood cells are normal. However the β-adrenoceptors show an age-dependent maturation process, which may account for an unresponsiveness to β-adrenoceptor agonists in wheezing infants.