Inhibition of human prostate smooth muscle contraction by the inhibitors of protein kinase C, GF109203X, and Go6983.
Humans
Indoles
/ pharmacology
Intracellular Signaling Peptides and Proteins
/ metabolism
Male
Maleimides
/ pharmacology
Muscle Contraction
/ drug effects
Muscle, Smooth
/ physiopathology
Prostate
/ metabolism
Prostatic Hyperplasia
/ drug therapy
Protein Kinase C
/ antagonists & inhibitors
Protein Kinase Inhibitors
/ pharmacology
benign prostatic hyperplasia (BPH)
lower urinary tract symptoms (LUTS)
prostate smooth muscle contraction
protein kinase C
α1-adrenoceptors
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
09
08
2021
received:
27
05
2021
accepted:
27
09
2021
pubmed:
12
10
2021
medline:
23
2
2022
entrez:
11
10
2021
Statut:
ppublish
Résumé
Prostate smooth muscle contraction is promoted by receptor-induced activation of intracellular signaling pathways. The presumed involvement in etiology and medical treatment of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) imparts a high clinical relevance to prostate smooth muscle contraction, which is contrasted by incomplete understanding at the molecular level. Involvement of protein kinase C (PKC) has been commonly assumed, but available studies were limited to nonhuman prostate smooth muscle or cell cultures. Here, we examined the effects of the PKC inhibitors Go6983 and GF109203x on contractions of human prostate tissues. Prostate tissues were obtained from radical prostatectomy. Contractions were induced by electric field stimulation (EFS), α GF109203X (500 nM) and Go6983 (300 nM) reduced EFS-, noradrenaline-, phenylephrine-, methoxamine-, and U46619-induced contractions of human prostate tissues, with maximum inhibitions approaching up to 55%. Using concentrations of 3 µM, GF109203X and Go6983 inhibited EFS- and noradrenaline-induced contractions, with similar effect sizes as 500 and 300 nM, respectively. Endothelin-1-induced contractions were not inhibited by GF109203X, and to neglectable extent by Go6983. After depolarization in calcium-free solution, calcium chloride-induced concentration-dependent contractions, which were inhibited by GF109203X and Go6983. GF109203X and Go6983 inhibit neurogenic, α
Substances chimiques
2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide
0
Indoles
0
Intracellular Signaling Peptides and Proteins
0
Maleimides
0
Protein Kinase Inhibitors
0
Protein Kinase C
EC 2.7.11.13
bisindolylmaleimide I
L79H6N0V6C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
59-77Informations de copyright
© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.
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