RT Journal Article
SR Electronic
T1 The soluble guanylyl cyclase activator YC-1 increases intracellular cGMP and cAMP via independent mechanisms
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.111.184135
DO 10.1124/jpet.111.184135
A1 Ramos-Espiritu, Lavoisier S
A1 Hess, Kenneth C
A1 Buck, Jochen
A1 Levin, Lonny R.
YR 2011
UL http://jpet.aspetjournals.org/content/early/2011/06/10/jpet.111.184135.abstract
AB In addition to increasing cGMP, the soluble guanylyl cyclase (sGC) activator 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1) can elevate intracellular cAMP levels. This response was assumed to be as a result of cGMP dependent inhibition of a cAMP phosphodiesterases (PDE); however, in this study we show that YC-1 induced cAMP production in the rat pancreatic beta cell line, INS-1E cells occurs independent of its function as sGC activator and independent of its ability to inhibit PDEs. This YC1-induced cAMP increase is dependent upon soluble adenylyl cyclase (sAC) and not on transmembrane adenylyl cyclase (tmAC) activity. We previously showed sAC-generated cAMP can lead to ERK activation, and YC-1 stimulated cAMP production also stimulates ERK. While 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.