Physiological modulation of intestinal motility by enteric dopaminergic neurons and the D2 receptor: analysis of dopamine receptor expression, location, development, and function in wild-type and knock-out mice

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Zhishan LiMichael D Gershon


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-D5 were analyzed by reverse transcription-PCR in stomach approximately duodenum approximately ileum approximately proximal > > distal colon. Dissected muscle and myenteric plexus contained transcripts encoding D1-D3 and D5, whereas mucosa contained D1 and D3-D5. D1-D5 expression 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 situ hybridization revealed that subsets of submucosal and myenteric neurons contained mRNA encoding D2 or D3. Immunoblots confirmed that D1, D2, and D5 receptor proteins were present from stomach through distal colon. Subsets of submucosal and myenteric neurons were also D1, D2, or D3 immunoreactive. When double labeled by in situ hybridization, 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 D2 plus D3. Both TGTT and CTT were decreas...Continue Reading


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