Serotonin in the rabbit ileum: Localization, uptake, and effect on motility

Abstract

Repeated experiments to localise serotonin in the myenteric plexus of rabbit ileum failed. After preincubation in serotonin (10 -5 M), an extensive varicose fibre system was detected by immunocytochemical methods. Stained fibres left the myenteric plexus and ran to the muscle layers. Labelled cell bodies could not be found, even after pretreatment with colchicine or pargyline. Application of reserpine (10 -5 M) and fluoxetine (10 -5 M) prevented serotonin uptake. Antisera against tryptophan hydroxylase revealed a rich fibre system, including those processes that entered the tertiary plexus. These fibres were able to accumulate serotonin, but again the cell bodies could not be detected. Serotonin caused concentrationdependent contraction in the longitudinal muscle layer of the rabbit ileum. Pretreatment with tetrodotoxin strongly reduced the effect of serotonin. Preapplication of atropine caused a slight decrease of response evoked by serotonin. Combined administration of tetrodotoxin and atropine significantly reduced the responses to serotonin, but did not abolish them. At the same time, agonists of 5-HT 2 and 5-HT 4 receptors caused concentration-dependent contractions. Our studies show that: 1) Without pretreatment, serotonin cannot be detected in the myenteric plexus of rabbit ileum. 2) An extensive uptake system works in this plexus. If released from myenteric nerve fibres, serotonin may evoke contractions in indirect and direct ways. 3) There may be an extrinsic serotoninergic innervation from the mesenteric ganglia. 4) Serotonin exerts its effect through 5-HT 2 and 5-HT 4 receptors on smooth muscle cells and nerve elements. Anat Rec Part A 271A: 368 -376, 2003.

Interactions of Serotoninergic, Cholinergic, and Tachykinin‐Containing Nerve Elements in the Rabbit Small Intestine

“…At the same time, coadministration of atropine (ATR) and tetrodotoxin (TTX) caused a further decrease in the response of longitudinal muscle (Dénes et al, 2003); thus, it is likely that noncholinergic nerve element(s) participate in mediating the effect of 5-HT. To test this hypothesis, we applied an NK1 receptor antagonist (N-acetyl-L-tryptophan-3,5(trifluoromethyl)-benzyl ester, 10 À7 M), which decreased the 5-HT-induced (10 À6 M) contractions significantly (Fig.…”

“…We reported previously that 5-HT 2 and 5-HT 4 receptors took part in the 5-HT-triggered contractions and that the response to alpha-methyl-5-hydroxytryptamine (a-m-5-HT, 10 À6 M) was decreased after preincubation with TTX (Dénes et al, 2003). We aimed at a more refined pharmacological dissection of these pathways.…”

“…In our previous article, data had been published about the serotoninergic system in rabbit (Dénes et al, 2003). Briefly, the 5-HT synthesizing enzyme could be detected in the myenteric plexus but before revealing a rich varicose 5-HT-IR fiber meshwork, we had to incubate the ileum with 5-HT.…”

“…Application of exogenous 5-HT caused a concentrationdependent increase of contractions in rabbit ileum. The results indicated that 5-HT could act directly on smooth muscle through 5-HT 4 and on neurons through 5-HT 2 receptors (Dénes et al, 2003).…”

“…In rabbit, however, 5-HT could be detected only after preloading in the myenteric plexus. Nevertheless, nerve fibers that could accumulate 5-HT were IR for tryptophan hydroxylase, the enzyme that synthesizes 5-HT (Dénes et al, 2003). Application of exogenous 5-HT caused a concentrationdependent increase of contractions in rabbit ileum.…”