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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.

Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L(-1)) or GLP-1 (10 nmol L(-1)) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1-400 pmol kg(-1) min(-1)) or GLP-1 (0.1-20 pmol kg(-1) min(-1)). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6-16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.