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 intracellular second messenger systems. Cyclic nucleotides such as cGMP, coupled to the recently discovered nitric oxide system, and cAMP are of outstanding interest in this respect. The present study used the modified Ussing chamber technique and mucins labelled with (SO4)-S-35 to investigate mucus secretion in the rat trachea to clarify the contribution of these different second 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 nitric oxide synthase nor the phosphodiesterase isoenzyme responsible for cGMP breakdown nor cGMP analogues were able to affect mucus secretion. In contrast, stimulation of adenylate cyclase or inhibition of the respective phosphodiesterase resulted in a potent increase of mucus secretion. In conclusion. we failed to show the involvement of the nitric oxide/cGMP system. whereas the cAMP system seems to be a very efficient regulator of mucus secretion in the rot trachea. (C) 2001 Elsevier Science B.V. All rights reserved.