Enteric neurons

GDNF Family - GDNF, NRTN, ARTN, and PSPN RET Alternative splicing results in three isoforms Required for enteric neuron development, kidney development, and spermatogenesis... 

TK NKxr displays a broad distribution in both peripheral tissues and in the central nervous system (CNS). In both CNS and enteric neurons, NKxr stimulation increase their excitability, whereas in trigeminal ganglion neurons SP has no intrinsic electrophysio-logical effects but is capable to enhance the amplitude of the inward current induced by the stimulation of serotonin 5-HT3 recqrtors. This enhancement dqjends on the activation of PKC via the stimulation of NKX recqrtors. This is an interesting case of receptor cross talk. Other functions of NKxr have been also highlighted. 

C. V, Douglas C.L., Jansen K., Lacy B.W., Cusack B., Richelson E. Specific gene blockade shows that peptide nucleic acids readily enter neuronal cells in vivo. FEBS Lett. 2000 421 280-284. 

Neurturin (NRTN) plays a critical role in supportingpara-sympathic neurons innervating peripheral target tissues. NRTN is required for the survival and function of enteric neurons and a subset of ganglionic sensory neurons, particularly those mediating temperature sensation. 

HT3 receptors are located exclusively on neurons and are widely distributed throughout the peripheral and central nervous systems. In the periphery, 5-HT3 receptors are found on autonomic, sensory, and enteric neurons (Fozard 1984). In the central nervous system, 5-HT3 receptors are labeled in cortex, hippocampus, caudate hypothalamus, brain stem, midbrain, and cerebellum, with the highest density in discrete nuclei of the lower brain stem (e.g., dorsal vagal complex and spinal trigeminal nucleus), the area postrema, and substantia gelatinosa at all levels of the spinal cord (Palacios et al. 1991 Waeber et al. 1989). 

Stimulation of 5-HT4 receptors on the presynaptic terminal of submucosal intrinsic primary afferent nerves enhances the release of their neurotransmitters, including calcitoningene-related peptide, which stimulate second-order enteric neurons to promote the peristaltic reflex (Figure 62-4). These enteric neurons stimulate proximal bowel contraction (via acetylcholine and substance P) and distal bowel relaxation (via nitric oxide and vasoactive intestinal peptide). 

Cannabinoid and endocannabinoid-induced synaptic depression is observed in both the peripheral nervous system and the CNS. Indeed, A9-THC inhibition of transmitter release was first demonstrated in mouse vas deferens (Graham et al. 1974), and further evidence for presynaptic inhibition has been obtained using this preparation (Ishac et al. 1996 Pertwee and Fernando 1996) and in the myenteric plexus (Coutts and Pertwee 1997 Kulkami-Narla and Brown 2000). In addition, anandamide was first characterized as an EC based on its actions in the mouse vas deferens (Devane et al. 1992). Subsequently, CB1 receptor-mediated inhibition of release of several neurotransmitters has been documented in various regions of the PNS (see Szabo and Schlicker 2005 for review). Cannabinoids also inhibit neural effects on contraction in the ileum (Croci et al. 1998 Lopez-Redondo et al. 1997), although it is not clear that this is effect involves direct inhibition of neurotransmitter release (Croci et al. 1998). The CB1 receptor has been localized to enteric neurons, and thus the effect on ileum certainly involves actions on these presynaptic neurons. In addition, anandamide produces ileal relaxation via a non-CBl, non-CB2-mediated mechanism (Mang et al. 2001). 

Fiorica-Howells E, Maroteaux L, Gershon MD. Serotonin and the 5-HT(2B) receptor in the development of enteric neurons. J Neurosci 2000 20 294-305. 

Pan H, Galligan JJ. 5-HT1A and 5-HT4 receptors mediate inhibition and facilitation of fast synaptic transmission in enteric neurons. Am J Physiol 1994 266 G230-G238. 

Electrophysiological Actions of Delta Opioid Agonists on Enteric Neurons... 

The columnar epithelial cells of the intestinal mucosa actively absorb and secrete extracellular ions, nutrients, and water. The active secretion of ions by these cells with an accompanying fluid flux acts to dilute and purge microorganisms or toxins in the bowel promotes the transfer of secretory immunoglobulin A, antimicrobial defensin peptides, and mucin into intestinal mucus and the gut lumen and, by affecting intraluminal pH, may alter the growth characteristics of enteric microflora [121]. Mucosal secretion is modulated by several enteric neurotransmitters, as well as inflammatory mediators released by mucosal mast cells that may affect transport indirectly through their ability to stimulate enteric neurons [122],... 

Verderio, C., Rossetto, O., Grumelli, C., Frassoni, C., Montecucco, C., Matteoli, M. (2006). Entering neurons botulinum toxins and synaptic vesicle recycling. EMBO Rep. 7 995-9. 

Metoclopramide is a first-generation benzamide. The drug acts presynaptically, mainly as a 5-hydroxytryptamine (5-HT serotonin) 5-HT4 receptor agonist and 5-HT3 receptor antagonist but it is also an antagonist at dopamine 1 (Dj) and 2 (D2) receptors (MacDonald 1991). The net effect of the interactions with these receptors is to facilitate acetylcholine release from enteric neurons and promote smooth muscle contrachon. Metoclopramide... 

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