Functional and biochemical modifications of lung beta-adrenoreceptors after in vivo desensitization: prevention by indomethacin.

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