The inhibitory effect of escitalopram on mouse detrusor contractility: The role of L-type calcium channels.

Autor: Engin S; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Türkiye. Electronic address: seckinengin@ktu.edu.tr., Barut EN; Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Türkiye., Erac Y; Department of Pharmacology, Faculty of Pharmacy, Ege University, İzmir, Türkiye., Sari S; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Türkiye., Kadioglu M; Department of Medical Pharmacology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Türkiye.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2023 Feb 15; Vol. 461, pp. 116408. Date of Electronic Publication: 2023 Feb 02.
DOI: 10.1016/j.taap.2023.116408
Abstrakt: Selective serotonin reuptake inhibitors (SSRIs) are associated with urinary problems attributed to their central effects. ESC is a preferred SSRI and several case reports described that ESC is related to urinary retention. However, the direct effect of ESC on detrusor contractility is still not completely elucidated. Thus, we investigated the effect of ESC on detrusor contractility and mechanism(s) of its action in isolated mouse detrusor strips. Molecular docking and measurement of intracellular calcium were performed to determine the possible calcium channel blocking effect of ESC. The contractile responses to carbachol (CCh), KCl and electrical field stimulation of detrusor strips were significantly abolished by ESC (10 or 100 μM). ESC relaxed KCl-precontracted detrusor strips concentration-dependently, which was not affected by tetraethylammonium, glibenclamide, 4-aminopyridine, propranolol, L-NAME or methylene blue. ESC (10 or 100 μM) reduced both the CaCl 2 - and CCh-induced contractions under calcium-free conditions, indicating the role of calcium-involved mechanisms in ESC-mediated relaxation. Furthermore, ESC significantly decreased Bay K8644-induced contraction and the cytosolic calcium level in fura-2-loaded A7r5 cells. Molecular docking study also revealed the potential of ESC to bind L-type calcium (Ca v 1) channels. Our results demonstrate that ESC inhibits detrusor contractility via blocking Ca v 1 channels, which provides evidence for the direct effect of ESC on detrusor contractility and its mechanism.
Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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