Tachykinins Stimulate Release of Peptide Hormones (Glucagon-Like Peptide-1) and Paracrine (Somatostatin) and Neurotransmitter (Vasoactive Intestinal Polypeptide) from Porcine Ileum Through NK-1 Receptors

The effects of infusion of the two tachykinins,substance P (SP) and neurokinin A (NKA), and ofcapsaicin on the release of glucagon-like peptide-1(GLP-1), somatostatin, and vasoactive intestinalpolypeptide (VIP) were studied in isolated, vascularlyperfused ileal segments. SP (10-8 M) stimulated GLP-1,somatostatin, and VIP release to 141.8 ± 6.6% (N= 18), 230.3 ± 38.7% (N = 21), and 359.7 ±60.5% (N = 22) of basal output, respectively. NKA(10 -8 M) only stimulated VIP release (to181.2 ± 16.7% of basal release, N = 22). Theeffects of SP and NKA were blocked by the NK-1 receptorantagonist CP96345 (10 -6 M). Infusion of atropine(10 -6 M) had no effect on the SP-inducedGLP-1 release, but partly inhibited the effect of SP onsomatostatin and VIP release, and the effect of NKA onVIP release. Capsaicin infusions (10 -5 M) significantlystimulated both GLP-1, somatostatin, and VIP release to111.1 ± 4.5% (N = 9), 138.0 ± 15.8% (N =9) and 208.3 ± 63.8% (N = 8) of basal release,respectively. Simultaneous addition of receptor antagonists to all threetachykinin receptors (CP96345, SR48968, and SR142801,all at 10 -6 M) significantly inhibited theeffect of capsaicin on VIP release, whereas the releaseof GLP-1 and somatostatin was unaffected. Weconclude that tachykinins potently stimulate the releaseof GLP-1, somatostatin, and VIP in the porcine ileum viaNK-1 receptors. The effect on somatostatin and VIP is partly mediated via cholinergic neurons.Sensory neurons releasing tachykinins could be involvedin the regulation of VIPergic neurons.