Effects of tachykinins and 5-hydroxytryptamine on intestinal secretion.
1. The main aim of the present study was to establish the functional in vivo effects of tachykinins on net fluid transport by the jejunum and ileum of anaesthetized rats. Tachykinins were administered by retrograde infusion in saline into the left common carotid artery. The possible involvement of 5-hydroxytryptamine (5-HT) in tachykinin-induced intestinal secretion was also investigated. 2. Some tachykinins were potent at reversing net absorption to secretion, particularly in the jejunum, where the rank order of potency was neurokinin (NK) A > substance P (SP) > NKB. The potency of the NK1 receptor-selective agonist [Sar9,Met(O2)11]-SP was the same as SP. Neurokinin A reduced net fluid absorption from the lumen of the jejunum at an intra-arterial infusion rate of 0.64 microg/kg per min. Infusions of NKA at 1.6 and 4 microg/kg per min induced net secretion into the lumen of the jejunum. These two higher infusion rates also affected fluid transport by the ileum, although not to the same extent as seen in the jejunum. The relative potency of SP was not affected by captopril (10 mg/kg, i.v.). 3. The secretory response of the jejunum to infusion of 4 microg/kg per min SP was blocked in animals administered the NK1 receptor antagonist SR 140 333 (1 mg/kg, i.v.). In addition, SR 140 333 blocked the secretory response to 4 microg/kg per min NKA. However, NKA still induced secretion in animals that had received the NK2 receptor antagonist SR 48 968 (0.3 mg/kg, i.v.). 4. A role for an endogenous tachykinin in the intestinal secretory action of 5-HT was not clearly established using the present model. Although SR 140 333 increased the absorption rate from the jejunum in animals infused intra-arterially with 5-HT, 5-HT itself did not cause a significant reduction in absorption. There were no significant differences in the absorption rates from the ileum between the control group and groups infused with 5-HT with and without SR 140 333. 5. The present study provides functional evidence for the existence of NK1 receptors in the rat small intestine, particularly in the proximal region, where their activation influences fluid transport. It is suggested that the presently used rat model is suitable for screening tachykinin antagonists for potential antidiarrhoeal activity.
D000818:Animals; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects* / Q000378:metabolism*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D015320:Tachykinins / Q000494:pharmacology*
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C085215:SR 140333; D012701:Serotonin