Treatment with high doses of terbutaline induces beta-adrenergic desensitization of guinea pig trachea not prevented by the addition of dexamethasone.
BACKGROUND
The combination of beta(2)-adrenergic agonists and glucocorticosteroids is frequently used to control bronchial asthma. It is believed that the co-administration of glucocorticosteroids will reduce the tachyphylaxis to beta(2)-adrenergic agonists.


OBJECTIVE
To analyse the effects of glucocorticosteroids on the response to high concentrations of beta(2)-adrenergic agonists.


METHODS
We have compared the effects of high doses of terbutaline, alone or in combination with dexamethasone, on the relaxation induced by in vitro beta(2)-adrenergic agonists in guinea pig trachea.


RESULTS
Terbutaline (100 mg/kg/day), for 7 days, induced a marked homologous desensitization. The addition of dexamethasone (0. 2 or 2 mg/kg/day) to the treatment did not prevent the development of desensitization, which was even more marked in the group treated with terbutaline and the higher doses of dexamethasone, compared with the group treated with terbutaline alone.


CONCLUSIONS
Our results suggest a negative interaction between high doses of beta(2)-adrenergic agonists and glucocorticosteroids in the airway smooth muscle of guinea pigs.
Seco
A J
AJ
Department of Medicine, Pharmacology, Faculty of Medicine, Oviedo, Spain.
Salgueiro
M E
ME
Villanueva
M A
MA
Manso
G
G
D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005938:Glucocorticoids / Q000008:administration & dosage; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D013726:Terbutaline / Q000008:administration & dosage* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D005938:Glucocorticoids; D003907:Dexamethasone; D002217:Carbachol; D013726:Terbutaline; D007213:Indomethacin