Short-term effect on intestinal epithelial Na+/H+ exchanger by Gi(alpha,1,2)-coupled 5-HT(1A)and G(q/11)-coupled 5-HT2 receptors

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Magro F (Author) FMUP; Sonia Fraga (Author) FFUP; soares-da-silva, p (Author) FMUP

Journal

Title: Life Sciences

Vol. 81

Pages: 560-569

ISSN: 0024-3205

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-004-8RT

DOI: 10.1016/j.lfs.2007.06.024

Abstract (EN): The present study evaluated the effect of 5-hydroxytryptamine (5-HT) on intestinal Na+/H+ exchanger (NHE) activity and the cellular signaling pathways involved in T84 cells. T84 cells express endogenous NHE I and NHE2 proteins, detected by immunoblotting, but not NHE3. The rank order for inhibition of NHE activity in acid-loaded T84 cells was 5-(N-ethyl-N-isopropyl)-amiloride(EIPA; IC50=519 [465, 579] nM)> cariporide (IC50=630 [484, 819] nM)> amiloride (IC50=19 [16, 24] mu M); the NHE3 inhibitor S3226 was found to be devoid of effect. This different inhibitory sensitivity indicates that both NHE1 and NHE2 isoforms may play an active role in Na+-dependent intracellular pH (pH(i)) recovery in T84 cells. Short-term exposure (0.5 h) of T84 cells to 5-HT increased NHE activity in a concentration-dependent manner. The stimulation induced by 5-HT (30 mu M) was partially inhibited by both WAY 100135 (300 nM) and ketanserin (300 nM), antagonists of 5-HT1A and 5-HT2 receptors, respectively. NHE activity was significantly increased by 8-OH-DPAT and alpha-methyl-5-HT, agonists of, respectively, 5-HT1A and 5-HT2 receptors. An incubation of T84 cell, with anti-G, and anti-G(beta) antibodies complexed with lipofectin did not prevent the 5-HT-induced stimulation of NHE activity. Overnight treatment with anti-G(i alpha 1,2) and anti-G(q/11) antibodies complexed with lipofectin blocked the stimulatory effect induced by 8-OH-DPAT and alpha-methyl-5-HT, respectively. It is concluded that in T84 cells 5-HT enhances intestinal NHE activity through stimulation of G(i alpha 1,2)-coupled 5-HT1A and G(q/11)-coupled 5-HT2 receptors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10