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.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007213:Indomethacin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007545:Isoproterenol / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014316:Tritium
D011943:Receptors, Adrenergic, beta; D014316:Tritium; D004082:Dihydroalprenolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D007213:Indomethacin