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Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: sildenafil and papaverin generate inhibition.
- Source :
-
The Prostate [Prostate] 2002 Apr 01; Vol. 51 (1), pp. 50-8. - Publication Year :
- 2002
-
Abstract
- Background: The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.<br />Methods: The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.<br />Results: LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 microM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50 = 2.5, and 0.35 microM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.<br />Conclusions: The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.<br /> (Copyright 2002 Wiley-Liss, Inc.)
- Subjects :
- Cell Division drug effects
Cells, Cultured
Colforsin pharmacology
Cyclic AMP metabolism
Cyclic AMP physiology
Cyclic GMP metabolism
Cyclic GMP physiology
DNA analysis
DNA biosynthesis
Dose-Response Relationship, Drug
Growth Inhibitors pharmacology
Humans
Lysophospholipids antagonists & inhibitors
Lysophospholipids physiology
Male
Muscle, Smooth pathology
Protein Biosynthesis
Proteins analysis
Purines
Purinones pharmacology
Sildenafil Citrate
Stimulation, Chemical
Sulfones
Lysophospholipids pharmacology
Muscle, Smooth drug effects
Papaverine pharmacology
Phosphodiesterase Inhibitors pharmacology
Piperazines pharmacology
Prostatic Hyperplasia pathology
Subjects
Details
- Language :
- English
- ISSN :
- 0270-4137
- Volume :
- 51
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 11920958
- Full Text :
- https://doi.org/10.1002/pros.10077