Introduction

The guanylate cyclase inhibitor LY-83583 is widely used to modulate the cyclic GMP signaling pathway, especially in addition to PKG inhibitors, in order to investigate the effects of inhibition.
However, some potential pitfalls were reported which should be known, in order to avoid drawbacks and disappointments:

 

Questionable Selectivity
LY-83583 seems not to be a really specific inhibitor of guanylate cyclase, since the following side effects have been reported:

• LY-83583 stimulates glucose transport independent of the cGMP pathway ¹

• LY-83583 inhibits the olfactory cyclic nucleotide-gated ion channel ²

 

Metabolic Fate
The metabolic fate of LY-83583 and the side effects of its metabolites in different tissues are unknown.

 

Conclusion
The guanylate cyclase inhibitor LY-83583 could be a useful additional control in concert with other tools, e.g. PKG inhibitors such as Rp-8-Br-PET-cGMPS, but should be used with caution and not be the single source of evidence for the involvement PKG.

 

Abbreviations:
LY-83583: {6-Anilino-5,8-quinolinequinone}

 

Selected references
The references shown were discovered by chance, no systematic survey has been made until now.

2	Leinders-Zufall, T.; Zufall, F., J.Neurophysiol., 74, 2759 - 2762 (1995): "Block of Cyclic Nucleotide-gated Channels in Salamander Olfactory Receptor Neurons by the Guanylyl Cyclase Inhibitor LY 83583"
1	Prasad, R.K.; Behrooz, A.; Ismail-Beigi, F., Eur. J. Pharmacol., 366, 101 - 109 (1999): "LY-83583 Stimulates Glucose Transporter-1-Mediated Glucose Transport Independent of Changes in cGMP Levels"