FUNCTIONAL AND BIOCHEMICAL MODIFICATIONS OF LUNG BETA-ADRENOCEPTORS AFTER INVIVO DESENSITIZATION - PREVENTION BY INDOMETHACIN

1 Desensitization of lung β-adrenoreceptors induced by 4 day in vivo isoprenaline administration to rats has been investigated both from a functional and a biochemical viewpoint. 2 Chronic isoprenaline treatment significantly reduced the relaxing activity of the β-agonist when tested ex vivo in lung parenchymal strips and also impaired the adenylate-cyclase system. Moreover, the desensitization procedure decreased by about 30% β-adrenoreceptor number. 3 In vivo indomethacin treatment prevented the loss of pharmacological responsiveness of the tissue to isoprenaline and restored basal adenylate-cyclase activity. 4 These data indicate that in vivo isoprenaline administration actually leads to pulmonary β-adrenoreceptor desensitization. The involvement of arachidonic acid metabolites in this phenomenon is also discussed.