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.
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References
Patel MS, Srinivasan M. Metabolic programming due to alterations in nutrition in the immediate postnatal period. J Nutr 2010;140:658–61.
Schäfer KH, Hänsgen A, Mestres P. Morphological changes of the myenteric plexus during early postnatal development of the rat. Anat Rec 1999;256:20–8.
Berseth CL. Gastrointestinal motility in the neonate. Clin Perinatol 1996;23:179–90.
Drozdowski LA, Clandinin T, Thomson AB. Ontogeny, growth and development of the small intestine: Understanding pediatric gastroenterology. World J Gastroenterol 2010;16:787–99.
Gershon MD. Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci 2010;33:446–56.
Hao MM, Young HM. Development of enteric neuron diversity. J Cell Mol Med 2009;13:1193–210.
de Vries P, Soret R, Suply E, Heloury Y, Neunlist M. Postnatal development of myenteric neurochemical phenotype and impact on neuromuscular transmission in the rat colon. Am J Physiol Gastrointest Liver Physiol 2010;299:G539–47.
Foong JP, Nguyen TV, Furness JB, Bornstein JC, Young HM. Myenteric neurons of the mouse small intestine undergo significant electrophysiological and morphological changes during postnatal development. J Physiol 2012;590:2375–90.
Chalazonitis A, Tang AA, Shang Y, et al. Homeodomain interacting protein kinase 2 regulates postnatal development of enteric dopaminergic neurons and glia via BMP signaling. J Neurosci 2011;31:13746–57.
Zizzo MG, Mulè F, Mastropaolo M, Serio R. D1 receptors play a major role in the dopamine modulation of mouse ileum contractility. Pharmacol Res 2010;61:371–8.
Li ZS, Schmauss C, Cuenca A, Ratcliffe E, Gershon MD. 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. J Neurosci 2006;26:2798–807.
Walker JK, Gainetdinov RR, Mangel AW, Caron MG, Shetzline MA. Mice lacking the dopamine transporter display altered regulation of distal colonic motility. Am J Physiol Gastrointest Liver Physiol 2000;279:G311–8.
Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 2011;63:182–217.
Hurley MJ, Mash DC, Jenner P. Dopamine D(1) receptor expression in human basal ganglia and changes in Parkinson’s disease. Brain Res Mol Brain Res 2001;87:271–9.
Jung AB, Bennett JP Jr . Development of striatal dopaminergic function. I. Pre- and postnatal development of mRNAs and binding sites for striatal D1 (D1a) and D2 (D2a) receptors. Brain Res Dev Brain Res 1996;94:109–20.
Kasirer MY, Welsh C, Pan J, Shifrin Y, Belik J. Metoclopramide does not increase gastric muscle contractility in newborn rats. Am J Physiol Gastrointest Liver Physiol 2014;306:G439–44.
Tonini M, Cipollina L, Poluzzi E, Crema F, Corazza GR, De Ponti F. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmacol Ther 2004;19:379–90.
Gershon MD. The play is still being written on opening day: postnatal maturation of enteric neurons may provide an opening for early life mischief. J Physiol 2012;590:2185–6.
Roberts RR, Ellis M, Gwynne RM, et al. The first intestinal motility patterns in fetal mice are not mediated by neurons or interstitial cells of Cajal. J Physiol 2010;588(Pt 7):1153–69.
Dawirs RR, Teuchert-Noodt G, Kampen WU. Demonstration of dopamine-immunoreactive cells in the gastrointestinal tract of gerbils (Meriones unguiculatus). J Histochem Cytochem 1992;40:1197–201.
Eisenhofer G, Aneman A, Friberg P, et al. Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab 1997;82:3864–71.
Kirschstein T, Dammann F, Klostermann J, et al. Dopamine induces contraction in the proximal, but relaxation in the distal rat isolated small intestine. Neurosci Lett 2009;465:21–6.
Furukawa K, Nomoto T. Postnatal changes in response to adenosine and adenine nucleotides in rat duodenum. Br J Pharmacol 1989;97:1111–8.
Miyazaki H, Ohga A, Saito K. Development of motor response to intramural nerve stimulation and to drugs in rat small intestine. Br J Pharmacol 1982;76:531–40.
Giaroni C, Knight GE, Zanetti E, et al. Postnatal development of P2 receptors in the murine gastrointestinal tract. Neuropharmacology 2006;50:690–704.
Tobón KE, Chang D, Kuzhikandathil EV. MicroRNA 142-3p mediates post-transcriptional regulation of D1 dopamine receptor expression. PLoS One 2012;7:e49288.
Pasuit JB, Li Z, Kuzhikandathil EV. Multi-modal regulation of endogenous D1 dopamine receptor expression and function in the CAD catecholaminergic cell line. J Neurochem 2004;89:1508–19.
Sahu A, Tyeryar KR, Vongtau HO, Sibley DR, Undieh AS. D5 dopamine receptors are required for dopaminergic activation of phospholipase C. Mol Pharmacol 2009;75:447–53.
Zizzo MG, Mastropaolo M, Grählert J, Mulè F, Serio R. Pharmacological characterization of uracil nucleotide-preferring P2Y receptors modulating intestinal motility: a study on mouse ileum. Purinergic Signal 2012;8:275–85.
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Zizzo, M., Cavallaro, G., Auteri, M. et al. Postnatal development of the dopaminergic signaling involved in the modulation of intestinal motility in mice. Pediatr Res 80, 440–447 (2016). https://doi.org/10.1038/pr.2016.91
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DOI: https://doi.org/10.1038/pr.2016.91
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