Authors: shafton, a. d.¹; bogeski, g.¹; kitchener, p. d.¹; sanger, g. j.²; furness, j. b.¹; shimizu, y.

Source: Neurogastroenterology and Motility, Volume 19, Number 7, July 2007 , pp. 617-624(8)

Publisher: Wiley-Blackwell

Abstract:

 

Antagonists of NMDA receptors can inhibit both the transmission of pain signals from the intestine and enteric reflexes. However, it is unknown whether doses of the NMDA antagonist, ketamine, that are used in anaesthetic mixtures suppress motility reflexes and visceromotor responses (VMRs). In fact, whether intestinal motility is affected by NMDA receptor blockers in vivo has been little investigated. We studied the effects of ketamine and memantine, administered intravenously or intrathecally. Rats were maintained under α-chloralose plus xylazine or pentobarbitone anaesthesia; VMR and jejunal motility were measured. Under α-chloralose/xylazine anaesthesia, i.v. ketamine inhibited VMRs at 6 mg kg h⁻¹, but not at 3 mg kg h⁻¹. It did not inhibit propulsive reflexes in the jejunum at 10 mg kg h⁻¹, but reduced them by 30% at 20 mg kg h⁻¹. Under α-chloralose/pentobarbitone anaesthesia, i.v. ketamine reduced propulsive reflexes at 40 mg kg h⁻¹ and VMR at 10 mg kg h⁻¹. Memantine inhibited VMRs at 20 mg kg h⁻¹ and propulsion at 2 mg kg h⁻¹. Ketamine and memantine, intrathecally, prevented VMRs, but not jejunal propulsion. We conclude that peripherally administered ketamine reduces both VMR and motility reflexes, but not at doses used in anaesthetic mixes (1.8-2.4 mg kg h⁻¹). Effects on motility reflexes are likely to be due to non-NMDA receptor actions, possibly on nicotinic receptors.

Keywords: intestinal motility; NMDA receptors; visceromotor reflexes

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2007.00942.x

Affiliations: 1: Department of Anatomy and Cell Biology, Centre for Neuroscience, University of Melbourne, Parkville, Vic., Australia 2: Neurology and GI CEDD, GlaxoSmithKline, New Frontiers Science Park, Harlow, UK

Publication date: 2007-07-01

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