Comparison of the Secretory Actions of 5-Hydroxytryptamine in the Proximal and Distal Colon of the Rat

Abstract

The ability of 5‐hydroxytryptamine (5‐HT) to induce a secretory response in rat proximal and distal colon was examined both in‐vivo and in‐vitro by measuring transintestinal electrical activity. In‐vivo 5‐HT caused a dose‐dependent increase in the potential difference (PD) in both regions of the colon (maximum PD change = 7·2 ± 0·5 (n = 17)mV in proximal colon and 9·2 ± 0·7 (n = 17)mV in distal colon), an effect that was also observed in stripped (outer muscle layers removed) colonic sheets where the PD change was found to result from a rise in short‐circuit current (SCC, maximum change = 150 ± 24 (n = 15)μA cm−2 in proximal colon and 126 ± 10 (n = 19)μA cm−2 in distal colon). The effects of 2‐methyl‐5‐hydroxytryptamine (2‐Me‐5‐HT), a relatively selective agonist at 5‐HT3 receptors, and 5‐methoxytryptamine (5‐MT), an agonist at all 5‐HT receptors except 5‐HT3, were also tested, their specificity of action being confirmed by their actions on cardiovascular function in‐vivo. 2‐Me‐5‐HT produced a similar response to 5‐HT in proximal colon, but was less effective in the distal region, particularly in‐vitro where it failed to induce any significant change in electrical activity. In contrast, 5‐MT was more effective in the distal colon. Frusemide (10−3 M) inhibited the rise in SCC induced by both 2‐Me‐5‐HT and 5‐MT, indicating that, like 5‐HT, these agonists stimulated electrogenic Cl· secretion. The 5‐HT3 antagonist granisetron abolished the effects of 2‐Me‐5‐HT, both in‐vivo (8·6 times 10−8 molkg−1) and in‐vitro (1·4 times 10−6M, 1·4 times 10−4M), but only caused a slight inhibition of the response to 5‐HT in‐vivo and no inhibition at all in stripped colonic sheets. It is concluded that although 5‐HT induces a secretory response in both proximal and distal colon, the mechanisms responsible differ, with 5‐HT3 receptors making a greater contribution in the proximal region.

The Action of 5-Hydroxytryptamine on Normal and Cystic Fibrosis Mouse Colon: Effects on Secretion and Intracellular Calcium

“…The basal electrical activity generated by colonic sheets from Swiss MF1 mice varied with the region of colon; lower PD and SCC values were observed in the more distal pair of tissues (Table 1). Similar ®ndings have been reported for the rat (Ayton et al 1995). Tissue resistance did not, however, differ in the two regions (Table 1).…”

“…In contrast, the 5-HT response in mouse colon does not seem to involve activation of neural pathways, because tetrodotoxin did not reduce the 5-HTinduced rise in SCC, and the 5-HT 3 agonist 1-phenylbiguanide, which acts solely via neural mechanisms (Hardcastle & Hardcastle 1997b), had little effect on the SCC. Similar ®ndings have been reported in rat distal colon (Ayton et al 1995). Other studies in rat (Siriwardena et al 1991) and guinea-pig (Cooke et al 1991) colon have, however, detected a tetrodotoxin-sensitive component in the electrical response to 5-HT, but it is possible that the region of colon tested was located more proximally than that used in the current investigation.…”

“…The electrophysiological studies con®rm that mouse colon, like that of rat (Zimmerman & Binder 1984;Bunce et al 1991;Siriwardena et al 1991;Ayton et al 1995) and guinea-pig (Cooke et al 1991) responds to 5-HT challenge with an increased SCC that is consistent with the stimulation Figure 1. Typical response of intact sheets of mouse colon to 5-HT (10 À4 M) challenge.…”

“…The mechanisms responsible, however, are still not fully understood; several factors contribute to this uncertainty. The 5-HT receptor population is complex, comprising numerous subtypes (Bradley et al 1986;Hoyer & Schoeffter 1991;Hoyer et al 1994), 5-HT has many possible sites of action within the intestine (Cooke 1994), and there are regional variations in the way the intestine responds to 5-HT challenge (Ayton et al 1995;Hardcastle & Hardcastle 1997a), and species differences (McLean et al 1995).…”

Regional Differences in Neurogenic Signal Transduction Pathway of Cholera Toxin‐Induced Fluid, Electrolyte and Serotonin Accumulation in the Porcine Jejunum

“…The 5-HT 3 receptor subtype, which is mainly located on neuronal structures, mediates secretion in vitro and in vivo in both jejunum, ileum and colon in several species (Hendriks et al 1989;Beubler et al 1992;Ayton et al 1995;Grøndahl et al 1996b). The present study demonstrates that within small distances of jejunum, differences exist in the role of 5-HT 3 receptors in the cholera toxin-induced secretory response.…”