Chemical coding of the human gastrointestinal nervous system: cholinergic, VIPergic, and catecholaminergic phenotypes.
The aim of this investigation was to identify the proportional neurochemical codes of enteric neurons and to determine the specific terminal fields of chemically defined nerve fibers in all parts of the human gastrointestinal (GI) tract. For this purpose, antibodies against the vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), vasoactive intestinal peptide (VIP), and protein gene product 9.5 (PGP 9.5) were used. For in situ hybridization (35)S-labeled VMAT1, VMAT2, and VAChT riboprobes were used. In all regions of the human GI tract, 50-70% of the neurons were cholinergic, as judged by staining for VAChT. The human gut unlike the rodent gut exhibits a cholinergic innervation, which is characterized by an extensive overlap with VIPergic innervation. Neurons containing VMAT2 constituted 14-20% of all intrinsic neurons in the upper GI tract, and there was an equal number of TH-positive neurons. In contrast, DBH was absent from intrinsic neurons. Cholinergic and monoaminergic phenotypes proved to be completely distinct phenotypes. In conclusion, the chemical coding of human enteric neurons reveals some similarities with that of other mammalian species, but also significant differences. VIP is a cholinergic cotransmitter in the intrinsic innervation of the human gut. The substantial overlap between VMAT2 and TH in enteric neurons indicates that the intrinsic catecholaminergic innervation is a stable component of the human GI tract throughout life. The absence of DBH from intrinsic catecholaminergic neurons indicates that these neurons have a dopaminergic phenotype.
Anlauf
Martin
M
Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University, Marburg, 35037 Marburg, Germany.
Schäfer
Martin K-H
MK
Eiden
Lee
L
Weihe
Eberhard
E
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000368:Aged; D001692:Biological Transport; D002352:Carrier Proteins / Q000032:analysis; D002395:Catecholamines / Q000032:analysis*; D002799:Cholinergic Fibers / Q000737:chemistry*; D004064:Digestive System / Q000737:chemistry* / Q000294:innervation*; D017615:Enteric Nervous System / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide / Q000032:analysis*; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; D002395:Catecholamines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; C493459:SLC18A3 protein, human; D050494:Vesicular Acetylcholine Transport Proteins; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D033921:Vesicular Transport Proteins; D014660:Vasoactive Intestinal Peptide; D000109:Acetylcholine