Effects of the nitric oxide/cGMP system compared with the cAMP system on airway mucus secretion in the rat

Mucus secretion of the airways is under the control of a variety of intrace llular second messenger systems. Cyclic nucleotides such as cGMP, coupled t o the recently discovered nitric oxide system, and cAMP are of outstanding interest in this respect. The present study used the modified Ussing chambe r technique and mucins labelled with (SO4)-S-35 to investigate mucus secret ion in the rat trachea to clarify the contribution of these different secon d messenger systems to the control of mucin secretion. A variety of drugs affecting tither the generation or the breakdown of the respective cyclic nucleotides were used. Neither drugs interfering with nit ric oxide synthase nor the phosphodiesterase isoenzyme responsible for cGMP breakdown nor cGMP analogues were able to affect mucus secretion. In contr ast, stimulation of adenylate cyclase or inhibition of the respective phosp hodiesterase resulted in a potent increase of mucus secretion. In conclusio n. we failed to show the involvement of the nitric oxide/cGMP system. where as the cAMP system seems to be a very efficient regulator of mucus secretio n in the rot trachea. (C) 2001 Elsevier Science B.V. All rights reserved.