ROLIPRAM REVERSED SALBUTAMOL TOLERANCE IN GUINEA PIG TRACHEA

Studies were carried out to examine the role of phosphodiesterase(PDE) III and PDE IV in the development of tachyphylaxis of isolated guinea pig trachea to β₂ adrenoceptor agonists. Treating trachea with salbutamol(SB) 1 μmol·L ^-1 for 1h produced a 5-fold rightward shift of the SB concentration response curve for the spasmolytic effect against methacholine induced bronchocon traction and decreased the maximum SB induced relaxation by 30%, i.e. induced tolerance of airway response of SB in vitro . The PDE IV inhibitor rolipram (Rol, 1 μmol·L^-1, IC₅₀), but not the PDE III inhibitor siguazodan (SK&F 94836, 1 μmol·L^-1, IC₅₀), reversed the SB tolerance. However, the protein synthesis inhibitor cycloheximide(10 μmol·L^-1) did not abolish the SB tolerance. These results indicate that the SB tolerance may be related to increase in PDE IV activity.