Effects of carvedilol on human prostate tissue contractility and stromal cell growth pointing to potential clinical implications.

Autor: Hu S; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Müderrisoglu AE; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Ciotkowska A; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Kale O; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Keller P; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Schott M; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Tamalunas A; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Waidelich R; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Stief CG; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany., Hennenberg M; Department of Urology, LMU University Hospital, LMU Munich, Munich, Germany. martin.hennenberg@med.uni-muenchen.de.; Urologische Klinik und Poliklinik, Marchioninistr. 15, 81377, Munich, Germany. martin.hennenberg@med.uni-muenchen.de.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2024 Aug; Vol. 76 (4), pp. 807-822. Date of Electronic Publication: 2024 Jun 11.
DOI: 10.1007/s43440-024-00605-5
Abstrakt: Background: Apart from antagonizing ß-adrenoceptors, carvedilol antagonizes vascular α 1 -adrenoceptors and activates G protein-independent signaling. Even though it is a commonly used antihypertensive and α 1 -adrenoceptors are essential for the treatment of voiding symptoms in benign prostatic hyperplasia, its actions in the human prostate are still unknown. Here, we examined carvedilol effects on contractions of human prostate tissues, and on stromal cell growth.
Methods: Contractions of prostate tissues from radical prostatectomy were induced by electric field stimulation (EFS) or α 1 -agonists. Growth-related functions were examined in cultured stromal cells.
Results: Concentration-response curves for phenylephrine, methoxamine and noradrenaline were right shifted by carvedilol (0.1-10 µM), around half a magnitude with 100 nM, half to one magnitude with 1 µM, and two magnitudes with 10 µM. Right shifts were reflected by increased EC 50 values for agonists, with unchanged E max values. EFS-induced contractions were reduced by 21-54% with 0.01-1 µM carvedilol, and by 94% by 10 µM. Colony numbers of stromal cells were increased by 500 nM, but reduced by 1-10 µM carvedilol, while all concentrations reduced colony size. Decreases in viability were time-dependent with 0.1-0.3 µM, but complete with 10 µM. Proliferation was slightly increased by 0.1-0.5 µM, but reduced with 1-10 µM.
Conclusions: Carvedilol antagonizes α 1 -adrenoceptors in the human prostate, starting with concentrations in ranges of known plasma levels. In vitro, effect sizes resemble those of α 1 -blockers used for the treatment of voiding symptoms, which requires concentrations beyond plasma levels. Bidirectional and dynamic effects on the growth of stromal cells may be attributed to "biased agonism".
(© 2024. The Author(s).)
Databáze: MEDLINE
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