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Soluble Guanylate Cyclase Modulators, BAY 41-2272 and BAY 60-2770, Inhibit Human and Rabbit Prostate Contractility

Soluble Guanylate Cyclase Modulators, BAY 41-2272 and BAY 60-2770, Inhibit Human and Rabbit Prostate Contractility

Fabiano B Calmasini, Eduardo C Alexandre, Fabio Henrique Silva, Gilberto De Nucci, Edson Antunes, Carlos A D'Ancona, Fabíola Z Mónica

Urology. 2016 Aug;94:312.e9-312.e15.

PMID: 27131967

Abstract:

Objective:
To evaluate the inhibitory effect of soluble guanylate cyclase (sGC) stimulator, BAY 41-2272 (5-cyclopropyl-2-[1-(2-fluorobenzyl)- 1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine) or activator, BAY 60-2770 (4-({(4- carboxybutyl) [2- (5-fluoro-2-{[40-(trifluoromethyl) biphenyl- 4-yl]methoxy}phenyl)ethyl] amino}methyl)benzoic acid), in human and rabbit prostate smooth muscle contractility.
Materials and methods:
In rabbit or human prostate, contractions induced by electrical field stimulation or phenylephrine (PE) were carried out in the presence of sGC stimulator, BAY 41-2272, or sGC activator, BAY 60-2770. The potency (pEC50) and maximal response (Emax) values were determined. Immunohistochemistry analysis for sGC α1-subunit and quantification of intracellular levels of cyclic guanosine monophosphate (cGMP) were also performed.
Results:
In rabbit prostate, BAY 60-2770 (30 and 300 nM) inhibited the contractions induced by PE and electrical field stimulation. The coincubation with sGC inhibitor, ODQ, produced greater inhibitions on PE-induced contractions in comparison with BAY 60-2770 alone, mainly due to greater cGMP accumulation (70- and 5.7-fold, respectively). BAY 41-2272 (300 nM) increased and decreased, respectively, cGMP levels and PE-induced contractions, but in the presence of ODQ these effects were reversed. In human prostate, immunohistochemistry analysis revealed the presence of sGC α1-subunit on the transition zone. BAY 60-2770 (300 nM) reduced significantly Emax induced by PE in human prostate.
Conclusion:
sGC activator seems to be a promising alternative to treat benign prostatic hyperplasia because it increases cGMP levels even when sGC is oxidized.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1027642438	BAY 60-2770		1027642-43-8	Price

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