Abstract
Purinergic P2X receptors contribute to neurotransmission in the gut. P2X receptors are ligand-gated cation channels that mediate synaptic excitation in subsets of enteric neurons. The present study evaluated colonic motility in vitro and in vivo in wild type (WT) and P2X2 and P2X3 subunit knockout (KO) mice. The muscarinic receptor agonist, bethanechol (0.3–3 μM), caused similar contractions of the longitudinal muscle in colon segments from WT, P2X2 and P2X3 subunit KO mice. Nicotine (1–300 μM), acting at neuronal nicotinic receptors, caused similar longitudinal muscle relaxations in colonic segments from WT and P2X2 and P2X3 subunit KO mice. Nicotine-induced relaxations were inhibited by nitro-l-arginine (NLA, 100 μM) and apamin (0.1 μM) which block inhibitory neuromuscular transmission. ATP (1–1000 μM) caused contractions only in the presence of NLA and apamin. ATP-induced contractions were similar in colon segments from WT, P2X2 and P2X3 KO mice. The mouse colon generates spontaneous migrating motor complexes (MMCs) in vitro. The MMC frequency was higher in P2X2 KO compared to WT tissues; other parameters of the MMC were similar in colon segments from WT, P2X2 and P2X3 KO mice. 5-Hydroxytryptophan-induced fecal output was similar in WT, P2X2 and P2X3 KO mice. These data indicate that nicotinic receptors are located predominately on inhibitory motor neurons supplying the longitudinal muscle in the mouse colon. P2X2 or P2X3 subunit containing receptors are not localized to motor neurons supplying the longitudinal muscle. Synaptic transmission mediated by P2X2 or P2X3 subunit containing receptors is not required for propulsive motility in the mouse colon.
Highlights
ATP is an excitatory and inhibitory neurotransmitter in the gastrointestinal tract (LePard et al, 1997; LePard and Galligan, 1999; Galligan et al, 2000; Nurgali et al, 2003; Serio et al, 2003)
The present study evaluated colonic motility in vitro and in vivo in wild type (WT) and P2X2 and P2X3 subunit knockout (KO) mice
Summary and conclusions Previous studies have shown that KO of P2X2 and P2X3 subunits causes impaired peristalsis in the mouse ileum maintained in vitro
Summary
ATP is an excitatory and inhibitory neurotransmitter in the gastrointestinal tract (LePard et al, 1997; LePard and Galligan, 1999; Galligan et al, 2000; Nurgali et al, 2003; Serio et al, 2003). P2X ionotropic receptors contribute to fast synaptic excitation in the small intestine and colon (Galligan and Bertrand, 1994; LePard et al, 1997; LePard and Galligan, 1999; Giaroni et al, 2002; Bian et al, 2003; Nurgali et al, 2003). Receptors containing P2X2 and P2X3 subunits have been localized to enteric neurons in the small intestine and colon where they contribute to fast synaptic excitation (Castelucci et al, 2002; Poole et al, 2002; Van Nassauw et al, 2002; Nurgali et al, 2003; Monro et al, 2004). The contribution of P2X receptor-mediated synaptic transmission to the colonic MMC has not been investigated
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