Observations Concerning the Action of 5‐hydroxytryptamine on the Peristaltic Reflex

Abstract

In isolated guinea-pig intestine 5-hydroxytryptamine increased the longitudinal muscle contractions in response to acetylcholine while the ganglionic action of nicotine was first facilitated and then blocked. Phenyldiguanide, veratrine, veratridine and protoveratrine, like 5-hydroxytryptamine, depressed the response to nicotine, leaving that to acetylcholine unaffected.The sensory stimulants, like 5-hydroxytryptamine, facilitated the peristaltic reflex when applied to the mucosa, and abolished it when applied to the serosa. Preceding the block, the initial effect of low concentrations of 5-hydroxytryptamine applied to the serosa was a short stimulation of peristalsis.Concentrations of 5-hydroxytryptamine which had an approximately equal stimulant action (mucosal 1 to 4 x 10-', serosal 2 to 8 X 10-8) were tested when various parts of the reflex arc were blocked. During block by procaine introduced into the lumen, mucosal application of 5-hydroxytryptamine re-established peristalsis, but serosal application of 5-hydroxytryptamine had no effect. During block by hexamethonium or atropine present in the bath, 5-hydroxytryptamine restored peristalsis more effectively by serosal application than by mucosal application. During block by serosal application of 5-hydroxytryptamine, morphine, phenoxybenzamine or dihydroergotamine, mucosal application of 5-hydroxytryptamine restored the peristaltic reflex while serosal application had no effect. During block by 2-bromo-lysergic acid diethylamide or lysergic acid diethylamide acting from the serosal surface, 5-hydroxytryptamine had no effect whether acting on the mucosal or on the serosal surface.It is concluded that 5-hydroxytryptamine facilitates the peristaltic reflex at two sites: when introduced into the lumen it stimulates mucosal sensory receptors; when acting from the serosal surface it sensitizes the muscle to the transmitter acetylcholine. There is also a transient stimulant action on the ganglia which is soon followed by inhibition; this indicates that 5-hydroxytryptamine applied to the serosa abolishes peristalsis by ganglion block.Two different actions of 5-hydroxytryptamine on the peristaltic reflex have recently been observed on isolated intestine of the guinea-pig. If 5-hydroxytryptamine was applied to the serosal surface, it inhibited peristalsis (Kosterlitz and Robinson, 1957; Ginzel, 1957); if it was applied to the mucosal surface it facilitated the peristaltic reflex (Bulbring and Lin, 1958;Lembeck, 1958). The stimulant action could be explained by the effect of 5-hydroxytryptamine on sensory receptors in the mucosa. The mechanism of the inhibitory action, however, when 5-hydroxytryptamine was applied to the serosa was not clear.It is known that a variety of substances stimulate not only chemoreceptors but also tension and stretch receptors in various organs (Dawes and Comroe, 1954; Iggo, 1957;Paintal, 1954Paintal, , 1957a and b). In the present investigation the action of some sensory stimulants, phenyldiguanide and veratrum alkaloids, has been compared w...

The effect of stimulation of extrinsic nerves on peristalsis and on the release of 5‐hydroxytryptamine in the large intestine of the guinea‐pig and of the rabbit

“…In a recent investigation Biilbring & Lin (1958) found that small amounts of 5-hydroxytryptamine (5-HT) were continuously released into the lumen of an isolated loop of ileum and that 5-HT, if applied intraluminally, stimulated peristalsis by its action on sensory receptors deeply seated in the intestinal mucosa. These findings have been extended by experiments on small intestine in situ (Bulbring & Crema, 1958, 1959a, but little is known about the effect of 5-HT on, and the release of 5-HT from, the large intestine. Moreover it is not known whether the release of 5-HT from the intestine is controlled by the extrinsic nerves.…”

Peripheral neural serotonin receptors: identification and characterization with specific antagonists and agonists.

“…In part, this uncertainty arises because 5-HT has many actions on the neurons, muscle, and epitheHum of the gut and it has been difficult to determine which of these are of physiological significance. The neuronal effects of 5-HT include excitation of mucosal afferent fibers to initiate the peristaltic reflex (4,5), a presynaptic inhibition of the release of acetylcholine (AcCho) from activated myenteric axons (6), stimulation of excitatory enteric neurons to cause a net release of AcCho resulting in smooth muscle contraction, and a relaxation of the bowel secondary to the activation of nonadrenergic, noncholinergic inhibitory neurons (7). Direct application of 5-HT onto myenteric type II/AH neurons may result in a rapid depolarization of the cells associated with an increase in membrane conductance (8), a slow depolarization associated with a decreased membrane conductance (9,10), a hyperpolarization associated with an increase in membrane conductance, or, with different time courses, all of these responses (11)(12)(13).…”

Serotonergic modulation of murine fundic tone

“…Additionally, in some species, including mice, mast cells contain 5-HT (4). It is well established that endogenous 5-HT released from mucosal EC cells activates intrinsic primary afferent neurons to initiate the peristaltic reflex in the small intestine (6,14). A similar pathway is proposed in the stomach: food stimulates mucosal EC cells, which in turn activate primary afferent neurons initiating gastric accommodation via the vagovagal reflex pathway.…”