Fast synaptic excitatory neurotransmission in the human submucosal plexus

Abstract

Background Acetylcholine is the main excitatory neurotransmitter in the enteric nervous system (ENS) in all animal models examined so far. However, data for the human ENS is scarce. Methods We used neuroimaging using voltage and calcium dyes, Ussing chamber, and immunohistochemistry to study fast synaptic neurotransmission in submucosal plexus neurons of the human gut. Key Results Electrical stimulation of intraganglionic fiber tracts led to fast excitatory postsynaptic potentials (fEPSPs) in 29 submucosal neurons which were all blocked by the nicotinic antagonist hexamethonium. The nicotinic agonist DMPP mimicked the effects of electrical stimulation and had excitatory effects on 56 of 73 neurons. The unselective NMDA antagonist MK‐801 blocked fEPSPs in 14 out of 22 neurons as well as nicotine evoked spike discharge. In contrast, the application of NMDA showed only weak effects on excitability or calcium transients. This agreed with the finding that the specific NMDA antagonist D‐APV reduced fEPSPs in only 1 out of 40 neurons. Application of AMPA or kainite had no effect in 41 neurons or evoked spike discharge in only one out of 41 neurons, respectively. Immunohistochemistry showed that 98.7 ± 2.4% of all submucosal neurons (n = 6 preparations, 1003 neurons) stained positive for the nicotinic receptor (α1, α2 or α3–subunit). Hexamethonium (200 µM) reduced nerve‐evoked chloride secretion by 34.3 ± 18.6% (n = 14 patients), whereas D‐APV had no effect. Conclusion & Inference Acetylcholine is the most important mediator of fast excitatory postsynaptic transmission in human submucous plexus neurons whereas glutamatergic fEPSPs were rarely encountered.

Enteric neuroanatomy and smooth muscle activity in the western diamondback rattlesnake (Crotalus atrox)

“…Apparently, the basal secretion of Ach in the case of the proximal stomach and the colon is insignificant, but it is released after stimulation also in these regions. The role of Ach as the main excitatory neurotransmitter in the snake is in accordance with findings in other species for example the fish [20], guinea pig and rabbit [21], and humans [22].…”

Changes in the Enteric Neurons Containing Selected Active Substances in the Porcine Descending Colon after the Administration of Bisphenol A (BPA)

“…The decrease in the number of GAL positive neurons noted in the present study is not in agreement with previous studies, in which BPA caused an increase in the number of neuronal cells containing GAL in the wall of the small intestine [ 10 , 12 ]. The reason for this difference is not clear, but on the one hand it may be connected with differences in GAL functions in various segments of the GI tract known from previous investigations [ 31 , 54 ], and on the other hand from undefined differences in the BPA impact between the small and large intestine.…”

“…In the light of previous studies, it is known that GAL plays multidirectional roles in the ENS, including the influence on secretion of other neurotransmitters from the enteric neurons, intestinal motility, and the secretory activity of the gastrointestinal mucosal layer [ 17 , 18 , 19 , 30 ]. In turn, a high level of neuronal cells immunoreactive to VAChT, which is the marker of cholinergic neurons, confirms a major role of acetylcholine—a key enteric neurotransmitter in the stimulation of intestinal motility and secretion [ 14 , 31 ]. Other substances studied in the present investigation, i.e., SP and VIP, are also involved in the regulation of various intestinal functions including intestinal motility, mucosal activity, immunological processes, blood flow, and sensory stimuli conduction [ 16 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…Therefore, the observed variations in the number of GAL-LI neurons may also be an effect of BPA-induced disorders in the functionality of the intestinal barrier. In turn, acetylcholine is the main neurotransmitter in the ENS under physiological conditions showing stimulatory activity [ 14 , 31 ]. The decrease in the number of GAL positive neurons noted in the present study is not in agreement with previous studies, in which BPA caused an increase in the number of neuronal cells containing GAL in the wall of the small intestine [ 10 , 12 ].…”