Inhibitory effect of theophylline, theophylline-7-acetic acid, ambroxol and ambroxol-theophylline-7-acetate on rat lung cAMP phosphodiesterase isoenzymes.
It is assumed that theophylline (THEO) and its xanthinic derivatives inhibit lung phosphodiesterase (PDE) and block adenosine receptors in the induction of bronchodilatation. Since the theophyllinic compound ambroxol-theophylline-7-acetic acid (ATA) has been shown in vivo to be a sound bronchodilator, this paper compares the action of ambroxol-theophylline-7-acetate (ATA), its two components, theophylline-7-acetic acid (TAA) and ambroxol (AMB), and theophylline (THEO) on the hydrolytic activity of three rat-lung cAMP PDE (types I, III and IV) and on striatal adenosine receptors. THEO inhibited all three isoenzymes with equal intensity, whereas ATA was as powerful but inhibited types III and IV only, on which AMB and TAA also showed lower effects. Lastly, unlike THEO, ATA and its two components were unable to antagonize adenosine receptors. Taken as a whole, these results suggest that the bronchodilating activity of ATA is the result of specific inhibition of particular forms of PDE and is thus more specific than that of THEO alone.
Ferretti
C
C
Institute of Pharmacology and Experimental Therapy, University of Turin, Italy.
Coppi
G
G
Blengio
M
M
Genazzani
E
E
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000551:Ambroxol / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D007527:Isoenzymes; D011983:Receptors, Purinergic; D014970:Xanthines; C077110:ambroxol-theophylline-7-acetate; D000551:Ambroxol; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C019140:acefylline