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


OBJECTIVE
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 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.


CONCLUSIONS
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.
Schmidt
P T
PT
Department of Medicine, Unit of Gastroenterology, Karolinska Hospital, Stockholm, Sweden. peter.thelin.schmidt@medks.ki.se
Lördal
M
M
Gazelius
B
B
Hellström
P M
PM
D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003971:Diastole; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects*; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects*; D017078:Laser-Doppler Flowmetry / Q000295:instrumentation / Q000379:methods; D008297:Male; D008365:Manometry; D016065:Myoelectric Complex, Migrating; D015288:Neurokinin A / Q000494:pharmacology*; D011674:Pulse; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D015288:Neurokinin A