The Effect of Low Dose 2-Agonists in Long Term Treatment of Cultured Human Leukocytes and Myometrial Cells
Document Type
Article
Publication Date
12-1-1996
Description
Long term treatment of preterm labor with z-adrenoceptor agonists such as terbutaline or ritodrine causes receptor desensitization and down regulation. In our ealier study, receptor density and cAMP production are decreased following exposure to 200nM terbutaline. This study examines whether this phenomenon is concentration-dependent using cultured myometrium and leukocytes exposed to lower therapeutic concentrations of terbutaline or ritodrine. Cells were incubated and exposed to either 10nM terbutaline or 56nM ritodrine for 0, 1 or 3 days. -Adrenoceptor binding was assessed using 125I-Pindolol. Basal and stimulated cAMP production were measured by RIA. Leukocytes and myometrial cells contained comparable adrenoceptors in terms of affinity and receptor density. After 3 days of incubation with either ritodrine or terbutaline, no change was noted in receptor density. Additionally cAMP production stimulated by isoproterenol, 10mM NaF, 24//M Forskolin, 10//M PGE-, did not change following exposure to agonists. Myometrial cells had higher basal cAMP production than leukocytes, but were not as highly stimulated by isoproterenol. The order of efficacy for cAMP production was: PGE, > Forskolin Isoproterenol > NaF. These results suggest that lower therapeutic concentrations of β-agonists do not change -adrenoceptor properties or the adenylyl cyclase-cAMP pathway. The order of efficacy for cAMP production suggests a complicated regulatory mechanisms between Gs and adenylyl cyclase in myometrial cells.
Citation Information
Liu, Yu L.J.; Mwosu, Uchenna C.; and Rice, Peter J.. 1996. The Effect of Low Dose 2-Agonists in Long Term Treatment of Cultured Human Leukocytes and Myometrial Cells. FASEB Journal. Vol.10(3). ISSN: 0892-6638