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Role of 5-HT₃ receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats

Liang-Wu Fu and John C. Longhurst

1. Activation of abdominal sympathetic afferents during ischaemia reflexly excites the cardiovascular system. We have shown previously that exogenous 5-hydroxytryptamine (5-HT, i.e. serotonin) stimulates abdominal sympathetic afferent nerve endings, and recently have documented increased concentrations of 5-HT in intestinal lymph and portal venous plasma during brief abdominal ischaemia. The present investigation evaluated the role of endogenously produced 5-HT in activation of ischaemically sensitive abdominal sympathetic afferents.

2. Nerve activity of single-unit C fibre afferents innervating duodenum, mesentery, pancreas, portal hepatis, bile duct, gall bladder and jejunum was recorded from the right thoracic sympathetic chain of anaesthetized cats. Ischaemically sensitive C fibre afferents were identified according to their response to 5-10 min of abdominal ischaemia.

3. Intra-arterial injection of 5-HT (20 µg kg^-1) increased discharge activity of twelve afferents from 0·23 ± 0·05 to 0·96 ± 0·09 impulses s^-1 after an onset latency of 5·7 ± 1·4 s. Also, 2-methylserotonin (100 µg kg^-1, i.a.), a 5-HT₃ receptor agonist, stimulated eleven of twelve afferents to significantly increase their discharge activity from 0·25 ± 0·05 to 0·90 ± 0·10 impulses s^-1 after a latency of 3·3 ± 0·4 s. Furthermore, intravenous injection of tropisetron (200 µg kg^-1), a 5-HT₃ receptor antagonist, significantly attenuated the increase in activity of twelve other C fibre afferents during 10 min of abdominal ischaemia from 1·62 ± 0·18 to 0·94 ± 0·22 impulses s^-1, and eliminated the response of eleven other afferents to 5-HT.

4. Both the 5-HT₂ receptor agonist, -methylserotonin (100 µg kg^-1, i.a.), and the 5-HT₁ receptor agonist, 5-carboxamidotryptamine (100 µg kg^-1, i.a.), did not alter the impulse activity of these twelve afferents (0·29 ± 0·05 to 0·31 ± 0·06, and 0·26 ± 0·06 to 0·29 ± 0·06 impulses s^-1, respectively).

5. Treatment with indomethacin (5 mg kg^-1, i.v.) in eight different cats did not alter the response of nine C fibre afferents to exogenous 5-HT (0·91 ± 0·17 vs. 1·19 ± 0·25 impulses s^-1, P > 0·05).

6. The results suggest that, during mesenteric ischaemia, endogenous 5-HT contributes to the activation of abdominal sympathetic afferents, mainly through direct stimulation of 5-HT₃ receptors and that the action of 5-HT on these afferents appears to be independent of the cyclo-oxygenase pathway.

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