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 of capsaicin on the release of glucagon-like peptide-1 (GLP-1), somatostatin, and vasoactive intestinal polypeptide (VIP) were studied in isolated, vascularly perfused 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 (to 181.2+/-16.7% of basal release, N = 22). The effects of SP and NKA were blocked by the NK-1 receptor antagonist CP96345 (10(-6) M). Infusion of atropine (10(-6) M) had no effect on the SP-induced GLP-1 release, but partly inhibited the effect of SP on somatostatin and VIP release, and the effect of NKA on VIP release. Capsaicin infusions (10(-5) M) significantly stimulated both GLP-1, somatostatin, and VIP release to 111.1+/-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 three tachykinin receptors (CP96345, SR48968, and SR142801, all at 10(-6) M) significantly inhibited the effect of capsaicin on VIP release, whereas the release of GLP-1 and somatostatin was unaffected. We conclude that tachykinins potently stimulate the release of GLP-1, somatostatin, and VIP in the porcine ileum via NK-1 receptors. The effect on somatostatin and VIP is partly mediated via cholinergic neurons. Sensory neurons releasing tachykinins could be involved in the regulation of VIPergic neurons.
Schmidt
P T
PT
Department of Medical Physiology, the Panum Institute, University of Copenhagen, Denmark.
Rickelt
L F
LF
Holst
J J
JJ
D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007082:Ileum / Q000294:innervation / Q000502:physiology*; D015288:Neurokinin A / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism*; D013268:Stimulation, Chemical; D013373:Substance P / Q000502:physiology*; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D010446:Peptide Fragments; D011498:Protein Precursors; D018040:Receptors, Neurokinin-1; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D015288:Neurokinin A; D052216:Glucagon-Like Peptide 1; D005934:Glucagon