Neural mechanisms underlying migrating motor complex formation in mouse isolated colon
Article first published online: 29 JAN 2009
2001 British Pharmacological Society
British Journal of Pharmacology
Volume 132, Issue 2, pages 507–517, January 2001
How to Cite
Brierley, S. M., Nichols, K., Grasby, D. J. and Waterman, S. A. (2001), Neural mechanisms underlying migrating motor complex formation in mouse isolated colon. British Journal of Pharmacology, 132: 507–517. doi: 10.1038/sj.bjp.0703814
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received May 26, 2000, Revised October 23, 2000, Accepted November 1, 2000)
- enteric nervous system;
- migrating motor complex;
- intestinal pacemakers
Little is known about the intrinsic enteric reflex pathways associated with migrating motor complex (MMC) formation. Acetylcholine (ACh) mediates the rapid component of the MMC, however a non-cholinergic component also exists. The present study investigated the possible role of endogenous tachykinins (TKs) in the formation of colonic MMCs and the relative roles of excitatory and inhibitory pathways.
MMCs were recorded from the circular muscle at four sites (proximal, proximal-mid, mid-distal and distal) along the mouse colon using force transducers.
The tachykinin (NK1 and NK2) receptor antagonists SR-140 333 (250 nM) and SR-48 968 (250 nM) reduced the amplitude of MMCs at all recording sites, preferentially abolishing the long duration contraction. Residual MMCs were abolished by the subsequent addition of atropine (1 μM).
The neuronal nitric oxide synthase inhibitor, Nωnitro-L-arginine (L-NOARG, 100 μM), increased MMC amplitude in the distal region, whilst reducing the amplitude in the proximal region. In preparations where MMCs did not migrate to the distal colon, addition of L-NOARG resulted in the formation of MMCs. Subsequent addition of apamin (250 nM) or suramin (100 μM) further increased MMC amplitude in the distal region, whilst suramin increased MMC amplitude in the mid-distal region. Apamin but not suramin reduced MMC amplitude in the proximal region. Subsequent addition of SR-140 333 and SR-48 968 reduced MMC amplitude at all sites. Residual MMCs were abolished by atropine (1 μM).
In conclusion, TKs, ACh, nitric oxide (NO) and ATP are involved in the neural mechanisms underlying the formation of MMCs in the mouse colon. Tachykinins mediate the long duration component of the MMC via NK1 and NK2 receptors. Inhibitory pathways may be involved in determining whether MMCs are formed.
British Journal of Pharmacology (2001) 132, 507–517; doi:10.1038/sj.bjp.0703814