Tachykinins potently stimulate human small bowel blood flow: a laser Doppler flowmetry study in humans

Abstract

Background: The two tachykinins substance P and neurokinin A are abundantly present in the gastrointestinal tract. Substance P preferring neurokinin 1 receptors are mainly found in submucosal blood vessels while neurokinin A preferring neurokinin 2 receptors seem to be confined to smooth muscle cells. Tachykinin effects on intestinal mucosal blood flow in humans are not known. Aim: To study the effects of substance P and neurokinin A on small bowel mucosal blood flow in humans. Methods: A manometry tube supplied with single fibre microprobes recorded mucosal blood flow in the proximal small bowel using laser Doppler flowmetry, concomitant with luminal manometry, defining phases I, II, and III of the migrating motor complex. Simultaneously, flowmetry of temporal skin was performed. Under fasting conditions saline was infused intravenously over four hours followed by infusion of substance P, neurokinin A, or saline. Results: During phase I, substance P 1-6 pmol/kg/min increased mucosal blood flow dose dependently by a maximum of 158%. Blood flow of the temporal skin increased in parallel. Neurokinin A 6-50 pmol/kg/min increased mucosal blood flow maximally by 86% at 25 pmol/kg/min while blood flow of temporal skin increased at all doses. Substance P at all doses and neurokinin A at the highest dose only, increased pulse rate. Systolic blood pressure was unchanged by either peptide while substance P at the highest dose decreased diastolic pressure. Conclusion: Tachykinins increase blood flow of the small bowel and temporal skin. With substance P being more potent than neurokinin A, these effects are probably mediated through neurokinin 1 receptors.

Dai-kenchu-to Raises Levels of Calcitonin Gene-Related Peptide and Substance P in Human Plasma

“…have recently reported that substance P increased mucosal blood flow of the small bowel blood dose dependently when infused intravenously into healthy subjects under fasting conditions. 23) Tachykininergic effects on blood flow seem to be primarily mediated by neurokinin 1 (NK1) receptors. In inflammatory bowel disease, a 1000-fold increase in the number of NK1 receptors on small bowel blood vessels has been described.…”

Comparison of the Effects of Pantethine and Fursultiamine on Plasma Gastrointestinal Peptide Levels in Healthy Volunteers

“…33) Furthermore administration of tachykinins/SP to healthy volunteers increased intestinal mucosal blood flow. 34) In our study, pantethine and fursultiamine had no significant effect on plasma SP-IS level. These suggest that SP may not be involved in the actions of pantethine and fursultiamine in increasing gastrointestinal motility and improving ileal function.…”

Effect of a Single Treatment with Keishininjinto on Plasma Levels of Gut-regulatory Peptides in Healthy Subjects

“…20) Various injuries factors such as neurotoxic capsaicin, which is the pungment ingredient in red peppers and a vanilloid receptor agonist, stimulates afferent sensory neurons called "capsaicin-sensitive afferent neurons," which release CGRP and substance P from their nerve endings. 19) These peptides enhance mucosal resistance to injuly via formation of vasodilation and hyperemia-independent mechanisms. The pathophysiological potential of this emergency system plays an important role in gastrointestinal cytoprotection.…”

“…18) Substance P also has been shown to increase in intestinal mucosal blood flow in humans. 19) Both CGRP and substance P are the major components of the afferent peptidergic innervation of the gastrointestinal tract, and are widely distributed around blood vessels. 20) Various injuries factors such as neurotoxic capsaicin, which is the pungment ingredient in red peppers and a vanilloid receptor agonist, stimulates afferent sensory neurons called "capsaicin-sensitive afferent neurons," which release CGRP and substance P from their nerve endings.…”