In this study, guinea pig tracheal smooth muscle pre-contracted with histamine was relaxed by the addition of 100 muM 8Br-cGMP, a non-hydrolyzable and cell-permeable analog for cGMP. This effect was not sensitive to cGMP-dependent protein kinase (PKG) inhibitors, whereas it was partially blocked by cAMP-dependent protein kinase (PKA) inhibitors. The relaxation observed was also reverted up to 50 +/- 8.5% by iberiotoxin, a selective inhibitor of large conductance, calcium-activated potassium channels (BKCa). Our results indicate that there exists a crosstalk mechanism between cAMP and cGMP signaling pathways which lead to relaxation of guinea pig tracheal smooth muscle and also that BKCa channels are involved to a certain extent in this phenomenon. (C) 2003 Elsevier Inc. All rights reserved.