© Copyright 2003 The British Pharmacological Society
University of Surrey
Summer Meeting June 2003
of fluoxetine on ellectrically-evoked contractions of the rat small
Mashhadi, F.A. Javid & R.J. Naylor, School of Pharmacy, University
of Bradford, Bradford BD7 1DP.
action of fluoxetine, citalopram and related agents is attributed to a
selective serotonin reuptake inhibition (SSRI). Recent studies suggest
that the SSRIs might have other effects not related to inhibition of neuronal
5-HT reuptake (Pacher et al., 2001). The aim of the present study
was to investigate the effect of fluoxetine on electrically- stimulated
tissues taken from the rat small intestine.
Segments (two cm length) taken from the duodenum, jejunum, mid ileum and
terminal ileum of male Lister Hooded rats (250-300 g) were mounted in
10 ml organ baths containing Krebs' solution (37°C, 95%O2,
5% CO2). The tissues were allowed to
equilibrate for 45 min and washed every 20 min. The resting tension was
maintained at 1 g and recorded isometrically. Electrical field stimulation
(EFS; 0.4, 1, and 10 Hz, 30 V and 0.5 ms pulse width, double pulses with
75ms delay, with a 10 min interval of stimulation) was delivered by means
of two platinum electrodes placed on either side of the tissue. Using
a paired experimental design, the tissues were exposed to EFS (1 min)
in the absence and presence of fluoxetine (10 nM, 0.1-10 µM). Tension
changes were expressed as the mean + s.e. mean of a control KCl (100µM)
- induced contraction; n=6 and data were analysed using the paired student's
EFS induced a frequency dependent contraction in all segments examined.
The contractile response to EFS at 1 Hz was significantly (p<0.05)
increased by 10 nM fluoxetine only in the segments taken from the duodenum.
The contractile response to EFS at 1 and 10 HZ were significantly (p<0.05,
0.001) attenuated by 1mm fluoxetine and abolished by 10 mM as compared
to the control tissues; 0.1 µM fluoxetine had no effect.
Figure 1- Representative
data showing the contractile response induced by electrical field stimulation
(30v, frequency 0.4,1 and 10 Hz, and 75 ms delay for 1 min) in the absence
and presence of 10 nM, 0.1-10 µM) fluoxetine in the duodenal segments
taken from the rat small intestine. *p<0.05, **p<0.01 and ***p<0.001
taken as significant differences compared to the control values.
The data suggest that fluoxetine at 10 nM may act as serotonin reuptake
inhibitor to increase the level of serotonin (Velasco et al., 1997)
leading to a greater size of contraction to EFS. However the ability of
fluoxetine to attenuate or abolish the contractile response to EFS could
be due to Ca2+ channel blocking actions
(Pacher et al, 2001) or antimuscarinic effect (Lucchelli et al., 1995). The latter effects of fluoxetine were achieved at concentrations
approximately 100 times greater than required to block 5-HT reuptake sites.
The significance of the effects of fluoxetine in the gut remains to be
Pacher P. et. al.(2001) Can. J. Physiol. Pharmacol. 79,
Lucchelli A. et. al. (1995) Br. J. Pharmacol. 114,
Velasco A. et. al. (1997) Gen. Pharmac. 28, 4, 509-512.