Neural involvement in 5-hydroxytryptamine-induced net electrogenic ion secretion in the rat intestine in-vivo

5-Hydroxytryptamine (5-HT) induces active electrogenic anion secretion by both the small intestine and the colon, responses that can be detected from measurements of transmural electrical activity. This approach was adopted to examine the involvement of neural mechanisms in 5-HT-induced secretion in rat proximal jejunum, distal ileum and proximal colon in-vivo. Under control conditions, 5-HT caused maximum rises in transintestinal potential difference of 4.7 +/- 0.3, 3.8 +/- 0.4 and 7.6 +/- 0.3 mV, respectively, with corresponding ED50 values of 28 +/- 3, 38 +/- 4 and 41 +/- 4 nmol kg-1 (n = 12). In each region examined a neural component in the secretory response to 5-HT was identified. Hexamethonium (22 mumol kg-1) reduced the 5-HT response in each region: in the jejunum and colon, it also attenuated the responses to the 5-HT3 agonist, phenylbiguanide and to 5-methoxytryptamine (5-MeOT), an agonist at all 5-HT receptors except 5-HT3, indicating that in these regions the nicotinic pathway can be activated by more than one 5-HT receptor subtype. Atropine (0.27 and 2.7 mumol kg-1) was found to have regional effects on the intestinal responses to 5-HT receptor agonists. In the jejunum, evidence for a pro-secretory muscarinic pathway which could be activated by more than one 5-HT receptor subtype was found. In the ileum and colon no muscarinic pro-secretory pathway was identified, indeed in the colon, an anti-secretory pathway may be present. This muscarinic anti-secretory pathway was observed with phenylbiguanide and 5-MeOT, but not 5-HT. Substance P release does not appear to be involved in mediating the intestinal secretory response to 5-HT. 5-HT-induced intestinal anion secretion may involve a direct secretory action on the enterocyte which can be modified by neurally-mediated pro-secretory and anti-secretory pathways, the balance between these processes varying down the length of the gut.