P2X7 receptors in the enteric nervous system of guinea-pig small intestine

The effects of anti-idiotypic antibodies (alpha-id) that recognize serotonin [5-hydroxytryptamine (5-HT)] receptors on myenteric neurons of the guinea pig small intestine were characterized electrophysiologically, and alpha-id binding sites were located immunocytochemically. Initial applications of the alpha-id mimicked each of three actions of 5-HT: a rapid depolarization, associated with a fall in input resistance (Rin), which was inhibited by the 5-HT3 antagonists tropisetron (> or = 1 microM) and renzapride (100 microM); a slow membrane depolarization, associated with increased Rin, that was inhibited by the 5-HT1P antagonist renzapride but was unaffected by a 5-HT4 blocking concentration of tropisetron (10 microM); and a hyperpolarization, associated with decreased Rin, that was antagonized by the 5-HT1A inhibitor NAN-190. Cross-desensitization was observed between responses to 5-HT and the alpha-id. After exposure to the alpha-id, subsequent responses to the alpha-id, 5-HT, and stimulus-evoked slow excitatory postsynaptic potentials were antagonized; however, responses to carbachol and substance P were unaffected. The alpha-id thus specifically inhibits the effects of endogenously released and exogenously applied 5-HT. The alpha-id bound to sites on myenteric and submucosal neurons and a subepithelial nerve plexus. Binding of the alpha-id was blocked by 5-HT1P-, 5-HT3-, and 5-HT4-specific antagonists. We concluded that the alpha-id binds selectively to all known subtypes of 5-HT receptor in the enteric nervous system and is thus useful for investigating the gastrointestinal function of 5-HT.

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Immunohistochemical study of choline acetyltransferase of a peripheral type (pChAT) in the enteric nervous system of rat and guinea pig

Neuroscience Research ◽

10.1016/s0168-0102(00)81191-8 ◽

2000 ◽

Vol 38 ◽

pp. S57 ◽

Cited By ~ 1

Author(s):

K Nakajima

Keyword(s):

Nervous System ◽

Guinea Pig ◽

Enteric Nervous System ◽

Choline Acetyltransferase ◽

Immunohistochemical Study ◽

Peripheral Type

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Dopamine Transporter Genetic Reduction Induces Morpho-Functional Changes in the Enteric Nervous System

Biomedicines ◽

10.3390/biomedicines9050465 ◽

2021 ◽

Vol 9 (5) ◽

pp. 465

Author(s):

Silvia Cerantola ◽

Valentina Caputi ◽

Gabriella Contarini ◽

Maddalena Mereu ◽

Antonella Bertazzo ◽

...

Keyword(s):

Nervous System ◽

Small Intestine ◽

Enteric Nervous System ◽

Dopamine Transporter ◽

Myenteric Plexus ◽

Receptor Activation ◽

D1 Receptor ◽

Functional Changes ◽

Neurochemical Coding ◽

The Impact

Antidopaminergic gastrointestinal prokinetics are indeed commonly used to treat gastrointestinal motility disorders, although the precise role of dopaminergic transmission in the gut is still unclear. Since dopamine transporter (DAT) is involved in several brain disorders by modulating extracellular dopamine in the central nervous system, this study evaluated the impact of DAT genetic reduction on the morpho-functional integrity of mouse small intestine enteric nervous system (ENS). In DAT heterozygous (DAT+/−) and wild-type (DAT+/+) mice (14 ± 2 weeks) alterations in small intestinal contractility were evaluated by isometrical assessment of neuromuscular responses to receptor and non-receptor-mediated stimuli. Changes in ENS integrity were studied by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (). DAT genetic reduction resulted in a significant increase in dopamine-mediated effects, primarily via D1 receptor activation, as well as in reduced cholinergic response, sustained by tachykininergic and glutamatergic neurotransmission via NMDA receptors. These functional anomalies were associated to architectural changes in the neurochemical coding and S100β immunoreactivity in small intestine myenteric plexus. Our study provides evidence that genetic-driven DAT defective activity determines anomalies in ENS architecture and neurochemical coding together with ileal dysmotility, highlighting the involvement of dopaminergic system in gut disorders, often associated to neurological conditions.

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