Naunyn-Schmiedeberg's archives of pharmacology
-
Naunyn Schmiedebergs Arch. Pharmacol. · Nov 2008
Role of the soluble guanylyl cyclase alpha1/alpha2 subunits in the relaxant effect of CO and CORM-2 in murine gastric fundus.
Carbon monoxide (CO) has been shown to cause enteric smooth muscle relaxation by activating soluble guanylyl cyclase (sGC). In gastric fundus, the sGCalpha1beta1 heterodimer is believed to be the most important isoform. The aim of our study was to investigate the role of the sGCalpha1/alpha2 subunits in the relaxant effect of CO and CORM-2 in murine gastric fundus using wild-type (WT) and sGCalpha1 knock-out (KO) mice. ⋯ Both in WT and sGCalpha1 KO mice, CO-evoked relaxations were associated with a significant cGMP increase; however, basal and CO-elicited cGMP levels were markedly lower in sGCalpha1 KO mice. These data indicate that besides the predominant sGCalpha1beta1 isoform, also the less abundantly expressed sGCalpha2beta1 isoform plays an important role in the relaxant effect of CO in murine gastric fundus; however, the sGC stimulator YC-1 loses its potentiating effect towards CO in sGCalpha1 KO mice. Prolonged administration of CO-either by the addition of CORM-2 or by continuous infusion of CO-mediates gastric fundus relaxation in both a sGC-dependent and sGC-independent manner.