Abstract

GUERRA DE GONZALEZ, L; GONZALEZ DE ALFONZO, R; LIPPO DE BECEMBERG, I  and  ALFONZO, M. Papel de las pde ic en la contracción del músculo liso de las vías aéreas: Futuras drogas broncorelajadoras. AVFT [online]. 2004, vol.23, n.2, pp.166-171. ISSN 0798-0264.

Muscarinic antagonists increase simultaneously and in a similar fashion the intracellular levels of cyclic nucleotides, in bovine tracheal smooth muscle. These original pharmacological responses were time-and dose-dependent, being maximal at 15 min, with pEC₅₀ (7.4 ± 0.2) for atropine Isobutylmethylxantine (IBMX 10 μM), a non-selective cyclic nucleotide phosphodiesterase (PDE) inhibitor, induced a similar effects suggesting the involvement of PDEs. Atropine enhanced the increments of cAMP levels induced by Rolipram and cGMP levels by Zaprinast. However, Vinpocetine (20 μM), a non-calmodulin dependent PDE Ic inhibitor was able to "mimic" these muscarinic antagonist responses. In cell free systems, muscarinic antagonists inhibit the membrane-bound PDE-Ic whereas the soluble (cytosol) PDE Ic was not affected. Thus muscarinic antagonists acting as "inverse agonists" on m2/m3 AChRs on sarcolema initiate a new signal cascade leading to PDE-Ic inhibition simultaneous rise in both cAMP and cGMP intracellular levels in tracheal smooth muscle.

Keywords : PDE; cGMP; cAMP; mAChR; Airways smooth muscle; Muscarinic antagonists.