[Experimental study on the action mechanism of a new bronchodilator agent, BB-1502].
The action mechanism of the bronchodilator activity of BB-1502 was studied in comparison with aminophylline. Orally administered BB-1502 did not inhibit passive cutaneous anaphylaxis in rats, an immediate allergic reaction of Type I, but strongly protected the same antigen-mediated anaphylactic asthma by the intraduodenal route, the activity being approximately 13 times more potent than that of aminophylline. BB-1502 also inhibited IgG-mediated anaphylactic asthma in guinea pigs by the oral route. Both IgE- and IgG-mediated histamine releases from rat lung were similarly inhibited by BB-1502, the potency being 2--3 times that of aminophylline. Disodium cromoglycate showed specific inhibition of the IgE-mediated reaction. BB-1502 and aminophylline showed nonspecific inhibition of the spasms of guinea pig ileum elicited by histamine, acetylcholine and BaCl2. Both compounds inhibited cyclic AMP and cyclic GMP phosphodiesterases (PDEs) derived from guinea pig organs. BB-1502 specifically inhibited the cyclic AMP PDE of lung and brain origins, while aminophylline showed no such specificity. The results of the present study suggested that the bronchodilator and anti-asthmatic actions of BB-1502 might, at least in part, be due to the regulation of cyclic nucleotide PDEs.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D001464:Barium / Q000037:antagonists & inhibitors; D017609:Barium Compounds; D001993:Bronchodilator Agents / Q000494:pharmacology*; D002712:Chlorides; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006633:Histamine Antagonists; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects*
D017609:Barium Compounds; D001993:Bronchodilator Agents; D002712:Chlorides; D006633:Histamine Antagonists; C024986:barium chloride; D001464:Barium; D000628:Aminophylline; C032993:9-cyclohexyl-2-n-propoxy-9H-adenine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000225:Adenine; D000109:Acetylcholine