[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 beta 2 adrenoceptor agonists. Treating trachea with salbutamol(SB) 1 mumol.L-1 for 1 h produced a 5-fold rightward shift of the SB concentration-response curve for the spasmolytic effect against methacholine-induced bronchocontraction 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 mumol.L-1, IC50), but not the PDE III inhibitor siguazodan (SK&F 94836, 1 mumol.L-1, IC50), reversed the SB tolerance. However, the protein synthesis inhibitor cycloheximide(10 mumol.L-1) did not abolish the SB tolerance. These results indicate that the SB tolerance may be related to increase in PDE IV activity.
Chen
J Q
JQ
Department of Pharmacology, Zhejiang Medical University, Hangzhou 310031.
Lu
Y B
YB
Zhou
H L
HL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology; D004361:Drug Tolerance; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D020889:Rolipram / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D010726:Phosphodiesterase Inhibitors; D020889:Rolipram; D000420:Albuterol