Rat gastrointestinal motor responses mediated via activation of neurokinin receptors.
Natural neurokinins (NK) and their specific receptor agonists, including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [NIe10]-NKA4-10 and senktide, were used to assess whether they could activate established NK receptors in rat gastrointestinal tract and central nervous system to alter gastric emptying or intestinal transit. Fasting rats were intubated with an orogastric catheter to feed them liquid radiochromium. Neurokinins and analogues (at 10(-10), 10(-9), 10(-8) and 10(-7) mol/kg) and vehicle (saline + 0.1% bovine serum albumin) were injected via an intraperitoneal route. Rats were killed 15 min later and the whole gut was removed. The radioactivity of the stomach and 10 equally divided small intestinal segments was counted to determine gastric emptying and the geometric centre of intestinal transit. Septide treatment at 10(-8) and 10(-7) mol/kg markedly delayed gastric emptying. All doses of NKA inhibited gastric emptying. However, other peptides did not influence gastric emptying. Both septide and NKB treatment at 10(-8) and 10(-7) mol/kg enhanced intestinal transit. Substance P or senktide treatment (10-(-7) mol/kg) also enhanced intestinal transit. Stasis of remaining radioactivity in the proximal intestine was found following SP, septide, NKA and NKB treatment, whereas accelerated transit in the distal intestine was induced following NKA, NKB and senktide treatment. In conclusion, the in vivo study of NK and their specific agonists manifests a selective influence of these compounds on rat gastrointestinal tract. This selective activation of stomach NK1 and NK2 receptors delays gastric emptying, whereas activation of intestinal NK1 and NK3 receptors enhances intestinal transit.
Division of Gastroenterology, Veterans General Hospital-Taipei, Taiwan, Republic of China. changfy@vghtpe.gov.tw
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Chang
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Yeh
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Wang
D000818:Animals; D002840:Chromates; D002860:Chromium Radioisotopes; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D007441:Intubation, Gastrointestinal; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000187:drug effects / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000187:drug effects / Q000502:physiology*; D017670:Sodium Compounds; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D002840:Chromates; D002860:Chromium Radioisotopes; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D017670:Sodium Compounds; C054724:senktide; D013373:Substance P; C028982:sodium chromate(VI); C054725:septide; D015288:Neurokinin A; D015287:Neurokinin B; D011761:Pyrrolidonecarboxylic Acid