Role of 5-HT3 receptors in activation of abdominal sympathetic C fibre afferents during ischaemia in cats.
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 microg 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 microg 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 microg 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, alpha-methylserotonin (100 microg kg-1, i.a.), and the 5-HT1 receptor agonist, 5-carboxamidotryptamine (100 microg 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.
Fu
L W
LW
Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California School of Medicine, Davis, CA 95616, USA. lwfu@ucdavis.edu
Longhurst
J C
JC
D000320:Adrenergic Fibers / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002415:Cats; D004594:Electrophysiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000098:blood supply / Q000166:cytology / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000378:metabolism / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis; D011985:Receptors, Serotonin / Q000502:physiology*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013152:Splanchnic Circulation; D000077526:Tropisetron; D014781:Viscera / Q000098:blood supply / Q000294:innervation
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007211:Indoles; D011453:Prostaglandins; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C042390:alpha-methylserotonin; D012701:Serotonin; D000077526:Tropisetron; C045918:2-methyl-5-HT; C047087:5-carboxamidotryptamine; D007213:Indomethacin