PT  - JOURNAL ARTICLE
AU  - Lavoisier S. Ramos-Espiritu
AU  - Kenneth C. Hess
AU  - Jochen Buck
AU  - Lonny R. Levin
TI  - The Soluble Guanylyl Cyclase Activator YC-1 Increases Intracellular cGMP and cAMP via Independent Mechanisms in INS-1E Cells
AID  - 10.1124/jpet.111.184135
DP  - 2011 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 925--931
VI  - 338
IP  - 3
4099  - http://jpet.aspetjournals.org/content/338/3/925.short
4100  - http://jpet.aspetjournals.org/content/338/3/925.full
SO  - J Pharmacol Exp Ther2011 Sep 01; 338
AB  - 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.