Soluble guanylate cyclase inhibitor prevents depression after moderate frequency stimulation and during cGMP-analogue treatment at the frog neuromuscular junction

Abstract

A guanylate cyclase pathway has been implicated in moderate frequency stimulus induced depression at the frog neuromuscular junction. This study sought to confirm this model by investigating the necessity of activation of soluble guanylate cyclase (sGC). A direct result of activation of sGC is the production of the guanosine 3,5- cyclic monophosphate (cGMP). Exogenous addition of membrane-permeant cGMP analogue 8-bromoguanosine- 3,5-cyclicmonophosphate (8-Br-cGMP) induced depression without moderate frequency stimulus. On the other hand, soluble guanylate cyclase inhibitor 6-anilino-5,8-quinolineone (LY-83583) was found to increase EPP amplitude following moderate frequency stimulus. It is concluded that soluble guanylate cyclase activation is necessary but not sufficient to induce depression under moderate frequency stimulation.