Effects of apafant on PAF-induced downregulation of beta-adrenoceptors in guinea pigs.
We examined the effects of platelet-activating factor (PAF) on beta-adrenoceptors and the functional response to isoproterenol in guinea pig parenchymal strips. PAF caused a reduction in the relaxation of guinea pig lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol. In addition, PAF decreased the density of beta-adrenoceptors in guinea pig lung without any change in the affinity. Apafant, a potent PAF antagonist, inhibited the above changes, indicating that it inhibited the downregulation of beta-adrenoceptors. These findings suggest that apafant may be effective in nonspecific airway hyperreactivity in asthma.
Sugimoto
Y
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Nakayama
Y
Y
Kishida
H
H
Hayakawa
T
T
Fujiwara
R
R
Kamei
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001667:Binding, Competitive; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D014230:Triazoles / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D001381:Azepines; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011943:Receptors, Adrenergic, beta; D014230:Triazoles; C052518:WEB 2086; D007545:Isoproterenol