The effect of a series of organic cations upon the plasmalemmal serotonin transporter, SERT

• Type: Article in International Scientific Journal
• Date: 2004

Authors

keating, e (Author) FMDUP; lemos, c (Author) Other; monteiro, r (Author) FCNAUP; azevedo, i (Author) Other; martel, f (Author) FMUP

Journal

Title: Life Sciences

Vol. 76 No. 24

Pages: 103-119

ISSN: 0024-3205

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 22 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-000-7PN

DOI: 10.1016/j.lfs.2004.08.007

Abstract (EN): The aim of this work was to test the effect of a series of organic cations upon the activity of the plasma membrane serotonin transporter (SERT). The experiments were performed using the JAR cell line that constitutively expresses high levels of SERT, and rat intestine, whose mucosal epithelial cells also express SERT. Initial rates of H-3-serotonin (H-3-5HT; 200 nM) uptake were not changed by some of the organic cations tested (guanidine, N-methylnicotinamide, choline, atenolol, caffeine and theophylline), but were slightly (15-30%) inhibited by some other organic cations, at the highest concentrations tested (thiamine (3 mM), cimetidine (1 mM) and tetraethylammonium (3 mM)). On the other hand, some other organic cations reduced, in a concentration-dependent manner, uptake of H-3-5HT by JAR cells (IC50S of 0.3, 1.3, 5.4, 89.3, 460 and 748 muM for quinidine, verapamil, propranolol, amiloride, nicotine and clonidine, respectively). Quinidine, clonidine and amiloride seem to be competitive inhibitors of H-3-5HT uptake, whereas verapamil, nicotine and propranolol appear to be uncompetitive or non-competitive inhibitors. Moreover, quinidine, verapamil and propranolol trans-inhibited H-3-5HT uptake, whereas clonidine, nicotine and amiloride were devoid of effect. Finally, these six organic cations were able to significantly increase the serosal-to-mucosal apparent permeability (P-app) to H-3-5HT of rat jejunum, ileum and colon. In conclusion, human and rat SERT-mediated transport is inhibited by several distinct organic cations, some of which are therapeutic agents or drugs of abuse. Knowledge on which organic cations interfere with SERT-mediated transport of 5HT will have major implications in tissues where 5HT plays important physiological roles (eg. central nervous system, intestine and placenta).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17