Proceedings of The Physiological Society
University College London 2006 (2006) Proc Physiol Soc 3, PC8
Effects of neurotensin on small intestinal afferent fibre activity in the rat
Holly Rossiter1, David C Bulmer1, Julia Smith1, Kevin Lee1, Wendy J Winchester1
1. Neurology and GI CEDD, GlaxoSmithKline, Harlow, United Kingdom.
The tridecapeptide neurotensin is located in high concentrations within specialised neuroendocrine cells (N cells) predominantly within the ileum. Neurotensin is released from the intestine in response to lipid infusion; however, the effects of neurotensin on extrinsic sensory nerves innervating the gut have not been characterised. Experiments were performed in male Sprague Dawley rats (300-450g) anaesthetised with sodium pentobarbitone (bolus 60 mg/kg i.p.; followed by 10-50 mg/kg/h i.v.). Femoral artery and vein were cannulated to facilitate the measurement of blood pressure and administration of anaesthetic, respectively. The jugular vein was cannulated for drug administration and the trachea cannulated to maintain a patent airway. A laparotomy was performed and a 5 cm segment of small intestine cannulated with saline-filled tubing. Resting intestinal pressure was raised to 2mmHg with saline. A mesenteric nerve bundle was dissected and attached to one pole of a platinum wire electrode with a strip of mesentery attached to the second pole. The nerve activity was amplified, filtered and recorded as a rate histogram. Changes from baseline in nerve activity and mean blood pressure are expressed as mean ± sem. Statistical comparisons were performed using Student’s paired t test. Neurotensin (3 nmol/kg i.v. n=5) elicited a robust increase in afferent activity (101.1 ± 10.6 spikes/s) and a decrease in mean blood pressure (46.3 ± 2.9 mmHg). A significant (p<0.05) desensitisation of the afferent fibre (70.6 ± 12.0 spikes/s) and depressor response (18.6 ± 3.8 mmHg) to neurotensin was observed following a second repeat injection. However, subsequent injections of neurotensin showed no further desensitisation enabling a dose-response relationship to be determined. Injection of increasing doses of neurotensin (0.1, 0.3, 1.0, 3.0 and 10 nmol/kg i.v., n=5) elicited a dose-related increase in afferent nerve activity with the exception of 10 nmol/kg at which no further increase was observed (e.g. 18.5 ± 3.0 spikes/s at 0.1 nmol/kg; 57.7 ± 4.6 spikes/s at 1.0 nmol/kg and 45.6 ± 4.2 spikes/s at 10 nmol/kg). The results of this study demonstrate that exogenous application of neurotensin excites visceral afferent fibres innervating the small intestine. These data support the hypothesis that neurotensin has a role in signalling sensory information from the gastrointestinal tract.
Where applicable, experiments conform with Society ethical requirements