ISSN:
1474-8673
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Chemistry and Pharmacology
,
Medicine
Notes:
1 The β3-adrenoceptor agonist ZD 7114, like the non-selective β-adrenoceptor agonist isoprenaline, but unlike the β1-adrenoceptor agonist dobutamine and the β2-adrenoceptor agonist salbutamol, produced an increment on mouse embryonic fibroblast proliferation. The half-maximal stimulation of cell growth occurred at substantially lower concentrations with the β3-adrenoceptor agonist (EC50: 5.5 × 10−8 m) than with isoprenaline (EC50: 1.25 × 10−6 m). 2 The selective β3-adrenoceptor antagonist SR 5923 OA prevented the β3-stimulated fibroblast proliferation. Conversely, practolol and butoxamine did not prevent fibroblast growth. 3 Additionally, a decrease of cAMP was obtained in fibroblasts cells upon stimulation with isoprenaline and ZD 7114. 4 The expression of β-adrenoreceptors on fibroblast cells was also studied by radioligand binding. The Ki values in the presence of β1- and β2-adrenoceptor antagonist was two-fold higher than the Ki values for β3 adrenoceptor antagonist indicating the presence of A3-receptor subtype. 5 Inhibitors of different intracellular coupling pathways including phospholipase C (U 73122), protein kinase C (staurosporine), calcium/calmodulin (trifluoroperazine) and calcium channel (verapamil), prevented the stimulatory actions of the selective β3-adrenoceptor agonist ZD 7114. 6 The presence of β3-adrenoceptors on embryonic mouse fibroblast cells may play a role in the modulation of cell growth and biologic activity. The mechanism by which ZD 7114 triggers cell proliferation and function, involves the activation of phospholipase C, PKC, calcium/calmodulin and the influx of calcium.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1474-8673.2002.00261.x
