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

Pediatric Research | Basic Science Investigation Print Share/bookmark Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice Maria Grazia Zizzo,Giacomo Cavallaro,Michelangelo Auteri,Gaetano Caldara,Ilaria Amodeo,Mariangela Mastropaolo,Domenico Nuzzo,Marta Di Carlo,Monica Fumagalli,Fabio Mosca,Flavia Mule& Rosa Serio Affiliations Corresponding author Pediatric Research (2016) 80, 440-447 doi:10.1038/pr.2016.91 Received 29 June 2015 Accepted 04 March 2016 Accepted article preview online 18 April 2016 Advance online publication 18 May 2016 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.