TY - JOUR T1 - The Soluble Guanylyl Cyclase Activator YC-1 Increases Intracellular cGMP and cAMP via Independent Mechanisms in INS-1E Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 925 LP - 931 DO - 10.1124/jpet.111.184135 VL - 338 IS - 3 AU - Lavoisier S. Ramos-Espiritu AU - Kenneth C. Hess AU - Jochen Buck AU - Lonny R. Levin Y1 - 2011/09/01 UR - http://jpet.aspetjournals.org/content/338/3/925.abstract N2 - In addition to increasing cGMP, the soluble guanylyl cyclase (sGC) activator 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) can elevate intracellular cAMP levels. This response was assumed to be as a result of cGMP-dependent inhibition of cAMP phosphodiesterases; however, in this study, we show that YC-1-induced cAMP production in the rat pancreatic beta cell line INS-1E occurs independent of its function as a sGC activator and independent of its ability to inhibit phosphodiesterases. This YC-1-induced cAMP increase is dependent upon soluble adenylyl cyclase and not on transmembrane adenylyl cyclase activity. We previously showed that soluble adenylyl cyclase-generated cAMP can lead to extracellular signal-regulated kinase activation and that YC-1-stimulated cAMP production also stimulates extracellular signal-regulated kinase. Although YC-1 has been used as a tool for investigating sGC and cGMP-mediated pathways, this study reveals cGMP-independent pharmacological actions of this compound. ER -