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

Abstract

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.

Opposite effects of dopamine on the mechanical activity of circular and longitudinal muscle of human colon

“…In the longitudinal layer, dopamine induces relaxation by acting on specific non‐neural D2‐like receptors leading to the increase of potassium conductance. Taken together our results indicate that, as in animal species, dopamine can be considered a modulator of intestinal contractility even in the human colon.…”

“…D1‐like receptor‐mediated dopaminergic response was inhibited by PLC/IP3 pathway blockers, as observed in mouse duodenum in postnatal period . D1‐like receptor family includes D1 and D5 receptors, sharing 80% sequence homology, which may differ for the related downstream signaling pathways, being D1, but not D5 receptors coupled to adenylate cyclase activation and D5 but not D1 receptors coupled to PLC pathway .…”

“…Dopamine‐induced inhibitory effects have been extensively reported in animal models, such as mouse, rat, and guinea‐pig intestine . Excitatory effects to DA have been occasionally observed as in guinea‐pig stomach or in mouse small intestine in the early postnatal age . However, in guinea‐pig stomach DA induced contractile effects via activation of adrenergic receptors, while in mouse small intestine DA interacts with its own receptors belonging to the D1‐like receptor family.…”

“…Evidence from animal studies supports a role of DA in the control gut motility . DA seems to induce mainly inhibitory effects, relaxing guinea‐pig and rat jejunum, mouse small intestine, and dog colon . DA, activating D1‐ or D2‐like receptors, inhibits electrically induced contractions of colonic muscle strips in rodents and it has an inhibitory effect on colonic peristaltic activity in guinea‐pig and rat .…”

Developmental and age-dependent plasticity of GABAA receptors in the mouse colon: Implications in colonic motility and inflammation

“…Interestingly, previous studies have shown that myenteric neurons of the intestine undergo significant morphological and electrophysiological changes from P 10 to adulthood (38). Indeed, neurotransmitter systems such as dopaminergic and purinergic system undergo developmental changes shifting from contraction to relaxation just before and during weaning (39,40). In addition, during these early postnatal days, the microbiota and immune cell community of the GIT are constantly changing (41,42).…”