Influences of Gender and Region on Responses to 5-HT in the Rat Small Intestine

Abstract

The aim of this study was to obtain more information regarding the ‘atypical’ 5-HT₇ receptor of the rat jejunum. 5-HT₇-induced contractions of the jejunum were elicited by 5-HT in the presence of ondansetron. Maximal responses were slightly larger in tissues from male compared to female rats of comparable age, with E_max values of 97.2 ± 3.3 and 84.25 ± 4.3% respectively compared to acetylcholine as an internal standard. However, the pEC₅₀valuesfor 5-HT were not significantly different. The mRNA expression levels of the 5-HT₇receptor were similar in whole jejunum and longitudinal muscle tissues taken from males and females. It was also shown that the maximal response of the jejunum from male rats was larger than the responses from mid intestine and ileum. However, in female tissues, the E_max of the mid intestine was significantly larger than the ileum, but not different from the jejunum. The results provide further insights into the ‘atypical’ 5-HT₇ receptor of the rat jejunum and are also useful in optimising the preparation for further studies.

Activation of 5‐HT3 receptors in the rat and mouse intestinal tract: a comparative study

“…The rat jejunum and ileum were used to establish the conditions for studying the 5‐HT 3 ‐induced responses by adding antagonists to the bathing solution to block nontarget 5‐HT receptors. The nontarget 5‐HT receptors are the 5‐HT 2A (Briejer et al ., 1997) and 5‐HT 4 receptors of the rat ileum (Tuladhar et al ., 1996) and colon (Kadowaki et al ., 2002) and the ‘atypical’ 5‐HT 7 receptor of the rat jejunum (McLean & Coupar, 1996; Liu et al ., 2004). Therefore, we investigated the effects of methysergide, which is an antagonist at 5‐HT 1,2,5,6,7 receptors (Hoyer et al ., 1994) and GR125487, which is a 5‐HT 4 receptor antagonist (Gale et al ., 1994) using the rat jejunum and ileum.…”

“…The fraction of the first curve was 0.57 with a pEC 50 of 7.13±0.09 ( n =8), whereas the pEC 50 of the second phase was 5.8±0.07 ( n =8). Previously, we had shown that the first phase is due to the activation of an ‘atypical’ 5‐HT 7 receptor population in the longitudinal muscle demonstrated by the presence of mRNA and functional properties (McLean & Coupar, 1996; Hemedah et al ., 1999; Liu et al ., 2004), whereas the second phase, shown at concentrations of 5‐HT above 1 μ M , is due to activation of neuronal 5‐HT 3 receptors (McLean & Coupar, 1996). Responses to 5‐HT were reduced by methysergide (1 μ M ) and GR125487 (0.1 μ M ) alone, but the combination of the antagonists at the same concentrations limited the 5‐HT response to a monophasic curve with an E max value of 35.72±1.6 and pEC 50 of 5.95±0.07 ( n =10, Figure 2a).…”

“…The tissues were placed in microcentrifuge tubes containing RNAlater™ (Ambion, Austin, TX, U.S.A.) then immediately frozen in liquid nitrogen and stored at −80°C. Frozen jejunum, ileum, proximal colon and distal colon tissues from six Hooded Wistar rats and six Swiss mice, of either sex, were homogenised with a pestle and mortar in liquid nitrogen for total RNA extraction and reverse transcription as described (Liu et al ., 2004). The quality of cDNA produced was assessed by amplifying cDNA for the house‐keeping gene, glyceraldehyde‐3‐phosphate dehydrogenase (G3PDH) using the following primers (forward: ; reverse: ) and the PCR products were separated on 2% agarose gels.…”

Comparison of 5-HT4 and 5-HT7 receptor expression and function in the circular muscle of the human colon

“…Alternatively, SB-269970 may be tissueselective. To illustrate this, we have found that SB-269970 does not inhibit 5-HT 7 -mediated contractions of the rat jejunum preparation (Liu, Irving and Coupar, unpublished results) even though whole tissues and longitudinal muscle showed the presence of mRNA for the r5-HT 7 receptor, particularly the r5-HT 7(a) and r5-HT 7(b) isoforms (Liu et al, 2004). However, this should be balanced against the generally agreed view that SB-269970 is not a species-selective antagonist.…”

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

“…When studying the 5-HT signaling pathway, important elements to examine include the number of EC cells, 5-HT content, tryptophan hydroxylase level, 5-hydroxyindoleacedic acid (HIAA), plasma 5-HT concentration and SERT expression [12] . Studies on animals and humans have measured the above elements in gastric and small intestinal mucosa and drawn some meaningful conclusions with regard to the mucosa 5-HT signaling pathway [13][14][15] . In this study, two important indicators, EC cells and 5-HT content, were used to study the small intestinal 5-HT signaling pathway in IBS patients.…”