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

Engin S., Barut E. N., Erac Y., Sari S., Kadioglu M.

TOXICOLOGY AND APPLIED PHARMACOLOGY, cilt.461, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 461
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1016/j.taap.2023.116408
  • Dergi Adı: TOXICOLOGY AND APPLIED PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Environment Index, Veterinary Science Database
  • Anahtar Kelimeler: Detrusor, Fura-2, Isolated organ bath, Molecular docking, Selective serotonin reuptake inhibitors, ACETYLCHOLINE-INDUCED CONTRACTIONS, URINARY-BLADDER, SMOOTH-MUSCLE, PROTEIN, ANTIDEPRESSANTS, RELAXATION, MANAGEMENT, RETENTION, ANXIETY
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

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 mu M). 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 mu M) reduced both the CaCl2- and CCh-induced contractions under calcium-free conditions, indicating the role of calcium-involved mechanisms in ESCmediated 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 (Cav1) channels. Our results demonstrate that ESC inhibits detrusor contractility via blocking Cav1 channels, which provides evidence for the direct effect of ESC on detrusor contractility and its mechanism.