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. 2008 Sep;4(3):255-66.
doi: 10.1007/s11302-007-9088-5. Epub 2007 Dec 8.

Purinergic receptors and synaptic transmission in enteric neurons

Jianhua Ren  1 , Paul P Bertrand
Affiliations

Purinergic receptors and synaptic transmission in enteric neurons

Jianhua Ren et al. Purinergic Signal. 2008 Sep.

Abstract

Purines such as ATP and adenosine participate in synaptic transmission in the enteric nervous system as neurotransmitters or neuromodulators. Purinergic receptors are localized on the cell bodies or nerve terminals of different functional classes of enteric neurons and, with other receptors, form unique receptor complements. Activation of purinergic receptors can regulate neuronal activity by depolarization, by regulating intracellular calcium, or by modulating second messenger pathways. Purinergic signaling between enteric neurons plays an important role in regulating specific enteric reflexes and overall gastrointestinal function. In the present article, we review evidence for purine receptors in the enteric nervous system, including P1 (adenosine) receptors and P2 (ATP) receptors. We will explore the role they play in mediating fast and slow synaptic transmission and in presynaptic inhibition of transmission. Finally, we will examine the molecular properties of the native receptors, their signaling mechanisms, and their role in gastrointestinal pathology.

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Figures

Fig. 1
Fig. 1
Diagram showing the major functional subtypes of neuron in the enteric nervous system. The major functional types are listed on the left and the two plexes, the myenteric and the submucosal, are listed at the top. Enteric sensory neurons are found in both the myenteric and submucosal plexes. The inhibitory (−) and excitatory (+) motor neurons to the circular (CM) and longitudinal (LM) smooth muscle are only found in the myenteric plexus while secretomotor neurons and vasodilator neurons are mainly found in the submucosal plexus. Ascending (Asc) and descending (Desc) interneurons are found in the myenteric plexus, while in the submucosal plexus, only a small population of local interneurons is found
Fig. 2a, b
Fig. 2a, b
Presynaptic inhibition of fast synaptic transmission in an S neuron in the submucous plexus of guinea pig ileum. a Left A fast EPSP was evoked by a single stimulus to an interganglionic fibre tract. Right Exposure to adenosine for 5 min suppressed the fast EPSP. b Left Depolarization to pressure application of DMPP (1 μM). Right During blockade of the fast EPSP, the depolarization to DMPP was unchanged in the presence of adenosine. Adapted from [114]. Copyright © Gastroenterology
Fig. 3a, b
Fig. 3a, b
Fast EPSPs in the myenteric and submucous plexes of the guinea pig ileum have a prominent purinergic component. a Pharmacologically distinct fast EPSPs from myenteric neurons. Left A fast EPSP that was blocked by the nicotinic-receptor antagonist hexamethonium (100 μM). Middle A fast EPSP that is partly reduced by hexamethonium and the rest is blocked by PPADS, an antagonist that blocks P2 receptors. Right A fast EPSP that is partly reduced by hexamethonium and is completely inhibited by the subsequent addition of the 5-HT-receptor antagonist ondansetron. Adapted from [115]. Copyright © Autonomic Neuroscience. b Pharmacologically distinct fast EPSPs from submucosal neurons. Left Application of the nicotinic-receptor antagonist hexamethonium (300 μM, Hex) abolished this fast EPSP. Middle In this neuron hexamethonium depressed the fast EPSP, and PPADS (10 μM) abolished the remainder. Right PPADS (10 μM) had no effect on this fast EPSP, but granisetron depressed it by approximately 50%. Adapted from [19]. Copyright © Journal of Physiology
Fig. 4a, b
Fig. 4a, b
Fast EPSPs in myenteric S neurons from mice deficient in P2X2 (A.) or P2X3 (B.) receptors. a Recordings from S neurons in P2X2+/+ (left) and P2X2−/− (right) mice. The fast EPSPs recorded from neurons in tissues from P2X2+/+ mice were inhibited by PPADS (10 μM) while those from neurons in P2X2-/- tissues were unaffected (right). b Fast EPSPs recorded from S neurons in P2X3+/+ (left) and P2X3−/− (right) mice; both were inhibited by PPADS (10 μM). Adapted from [78, 89]. Copyright © Journal of Physiology
Fig. 5a, b
Fig. 5a, b
Slow EPSPs in the submucous plexus of guinea pig ileum are blocked by P2Y receptor antagonists. Voltage traces taken from two submucosal neurons. a A single-pulse electrical stimulus evoked, in the following order: a fast EPSP, an intermediate EPSP, a small IPSP and a slow EPSP. Application of the P2-receptor antagonist PPADS (30 μM, middle trace) abolished the slow EPSP. Note, the IPSP amplitude is enhanced in the middle trace by the blockade of the intermediate EPSP and the slow EPSP. b The selective P2Y1-receptor antagonist MRS 2179 (10 μM) abolished the slow EPSP while the fast EPSP was spared. The IPSP in this cell had already been blocked with idazoxan. Adapted from [19]. Copyright © Journal of Physiology
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