POTENTIATION OF 5-HYDROXYTRYPTAMINE (5-HT) RESPONSES BY A 5-HT UPTAKE INHIBITOR, CITALOPRAM, IN HUMAN UMBILICAL ARTERY.

ERRASTI A, ARMESTO A, DEL REY G, ROTHLIN R.

Rosario, Provincia de Santa Fe, Argentina.

Congreso; XLI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2009

Asociación Argentina de Farmacología Experimental (SAFE)

potentiation of 5-hydroxytryptamine (5-HT) responses by a 5-HT uptake inhibitor, citalopram, in human umbilical artery. Errasti A, Armesto A, Del Rey G, Rothlin R. III Cátedra de Farmacologia, Facultad de Medicina, Universidad de Buenos Aires. farmaco3@fmed.uba.ar. Introduction: 5-HT contracts the human umbilical artery (HUA) and mediates its effects through 5-HT2A and 5-HT1B receptors. 5-HT is taken up into cells via the specific serotonin transporter (SERT); therefore, the aim was to evaluate the effects of the SERT inhibitor, citalopram, on contractions to 5-HT in HUA. Methods: HUA rings were mounted in isolated organ baths and after 2hs equilibration period, were incubated with or without citalopram for 30 min. Then, concentration response-curves (CRC) to 5-HT were constructed. Results: citalopram (10 nM) increased the potency of CCR to 5-HT (control, 7.76 ± 0.01; treated, 8.12 ± 0.01, n=7, p<0.05) without modification of maximal response (control, 3.62 ± 0.48g; treated, 3.27 ± 0.46). Citalopram (100 nM) caused no further increase either in potency or efficacy. On the other hand, citalopram (1 µM) induced a parallel rightward shift without modification of maximal response of the CCR to 5-HT (7.27 ± 0.01, n=7, p<0.05, pKB=6.33 ± 0.11). Conclusion: the lower concentration of citalopram increases the potency of 5-HT compatible with its 5-HT re-uptake inhibitory value (IC50: 1.8 nM) indicating that SERT inhibition could be involved in HUA. The higher concentration of citalopram inhibits 5-HT responses in HUA with an estimated pKB of 6.33, probably due to citalopram inhibiting 5-HT2A receptor at this concentration (pKi=5.25).