RETRACTED ARTICLE: ß2-adrenoreceptor Inverse Agonist Down-regulates Muscarine Cholinergic Subtype-3 Receptor and Its Downstream Signal Pathways in Airway Smooth Muscle Cells in vitro

Abstract

Abstract Mechanisms underlying ß2-adrenoreceptor (ß2AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLCß1 and IP3. The level of M3R in the presence of 10-5?mmol/L ICI118,551 were significantly decreased at 12?h, 24?h and 48?h (P?<?0.05), and at 24?h were significantly reduced in ICI118,551 with concentration of 10-5mmol/L, 10-6mmol/L, 10-7mmol/L, and 10-8mmol/L (P?<?0.05). The level of IP3 in 10-5mmol/L ICI118,551 was significantly diminished at 24?h (P?<?0.01), except for that at 1?h, neither was in the level of PLCß1. A concentration of 10-5mmol/L ICI118,551 at 24?h showed a significant reduction of M3R level compared to formoterol (P?<?0.01), budesonide (P?<?0.01), and formoterol?+?budesonide (P?<?0.05), but significant reduction of PLCß1 and IP3 was only found between 10-5mmol/L ICI118,551 and formoterol at 24?h, but not in the comparison of budesonide or formoterol?+?budesonide. Pindolol and H89 could not inhibit the formoterol-induced expression of M3R (P?>?0.05), but SQ22,536 significantly antagonized the formoterol-induced M3R expression (P?<?0.05). In conclusions, ß2AR inverse agonist, ICI118,551, exerts similar bronchoprotective effects to corticosteroids via decreasing the expression of M3R and inhibiting the production of IP3.