Physiological Modulation of Intestinal Motility by Enteric Dopaminergic Neurons and the D2Receptor: Analysis of Dopamine Receptor Expression, Location, Development, and Function in Wild-Type and Knock-Out Mice
| Autor: | Michael D. Gershon, Abigail Cuenca, Zhi Shan Li, Elyanne M. Ratcliffe, Claudia Schmauss |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
Time Factors Dopamine Blotting Western Drinking Gene Expression Motility In situ hybridization Biology Eating Mice Dopamine receptor D2 Internal medicine medicine Animals Immunoprecipitation RNA Messenger Receptor In Situ Hybridization Myenteric plexus Mice Knockout Neurons Analysis of Variance Dopamine Plasma Membrane Transport Proteins Receptors Dopamine D2 Reverse Transcriptase Polymerase Chain Reaction General Neuroscience Dopaminergic Receptors Dopamine D3 Gene Expression Regulation Developmental Articles Embryo Mammalian Gastrointestinal Tract Mice Inbred C57BL Endocrinology Animals Newborn Dopamine receptor Enteric nervous system Gastrointestinal Motility |
| Zdroj: | The Journal of Neuroscience. 26:2798-2807 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.4720-05.2006 |
| Popis: | Dopaminergic neurons are present in both plexuses of the murine bowel and are upregulated after extrinsic denervation but play unknown roles in enteric nervous system (ENS) physiology. Transcripts encoding dopamine (DA) receptors D1–D5were analyzed by reverse transcription-PCR in stomach ≈ duodenum ≈ ileum ≈ proximal ≫ distal colon. Dissected muscle and myenteric plexus contained transcripts encoding D1–D3and D5, whereas mucosa contained D1and D3–D5. D1–D5expression began in fetal gut [embryonic day 10 (E10)], before the appearance of neurons (E12), and was sustained without developmental regulation through postnatal day 1.In situhybridization revealed that subsets of submucosal and myenteric neurons contained mRNA encoding D2or D3. Immunoblots confirmed that D1, D2, and D5receptor proteins were present from stomach through distal colon. Subsets of submucosal and myenteric neurons were also D1, D2, or D3immunoreactive. When double labeled byin situhybridization, these neurons contained mRNA encoding the respective receptors. Total gastrointestinal transit time (TGTT) and colonic transit time (CTT) were measured in mice lacking D2, D3, or D2plus D3. Both TGTT and CTT were decreased significantly (motility increased) in D2and D2plus D3, but not D3, knock-out animals. Mice lacking D2and D2plus D3but not D3were smaller than wild-type littermates, yet ate significantly more and had greater stool frequency, water content, and mass. Because motility is abnormal when D2is absent, the net inhibitory DA effect on motility is physiologically significant. The early expression of DA receptors is also consistent with the possibility that DA affects ENS development. |
| Databáze: | OpenAIRE |
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