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Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice

  • Autori: Zizzo, M.; Cavallaro, G.; Auteri, M.; Caldara, G.; Amodeo, I.; Mastropaolo, M.; Nuzzo, D.; Di Carlo, M.; Fumagalli, M.; Mosca, F.; Mule, F.; Serio, R.
  • Anno di pubblicazione: 2016
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: Pediatrics, Perinatology and Child Health
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Background:Since antidopaminergic drugs are pharmacological agents employed in the management of gastrointestinal motor disorders at all ages, we investigated whether the enteric dopaminergic system may undergo developmental changes after birth.Methods:Intestinal mechanical activity was examined in vitro as changes in isometric tension.Results:In 2-d-old (P2) mice, dopamine induced a contractile effect, decreasing in intensity with age, replaced, at the weaning (day 20), by a relaxant response. Both responses were tetrodotoxin (TTX)-insensitive. In P2, dopaminergic contraction was inhibited by D1-like receptor antagonist and mimicked by D1-like receptor agonist. In 90-d-old (P90) mice, the relaxation was reduced by both D1- and D2-like receptor antagonists, and mimicked by D1- and D2-like receptor agonists. In P2, contraction was antagonized by phospholipase C inhibitor, while in P90 relaxation was antagonized by adenylyl cyclase inhibitor and potentiated by phospholipase C inhibitor. The presence of dopamine receptors was assessed by immunofluorescence. Quantitative real-time polymerase chain reaction (qRT-PCR) revealed a significant increase in D1, D2, and D3 receptor expression in proximal intestine with the age.Conclusion:In mouse small intestine, the response to dopamine undergoes developmental changes shifting from contraction to relaxation at weaning, as the consequence of D2-like receptor recruitment and increased expression of D1 receptors.