Mas-related G protein-coupled receptor D is involved in modulation of murine gastrointestinal motility

What is the central question of this study? The physiological function of Mas-related G protein-coupled receptor D (MrgprD) in gastrointestinal motility is unknown. The aim of this study was to assess the effects of MrgprD and its receptor agonists on murine gastrointestinal motility. What is the main finding and its importance? Mrgprd deficiency improved murine gastrointestinal motility in vivo but had no effects on the spontaneous contractions of murine intestinal rings ex vivo. Systemic administration of the MrgprD ligand, either β-alanine or alamandine, delayed gastrointestinal transit in vivo and attenuated the spontaneous contractions of isolated intestinal rings ex vivo.

Mas-related G protein-coupled receptor D (MrgprD) was first identified in sensory neurons of mouse dorsal root ganglion and has been demonstrated to be involved in sensations of pain and itch. Although expression of MrgprD has recently been found in the gastrointestinal (GI) tract, its physiological role in GI motility is unknown. To address this question, we used Mrgprd knockout (Mrgprd^-/- ) mice and MrgprD agonists to examine the effects of Mrgprd gene deletion and MrgprD signalling activation, respectively, on murine intestinal motility, both in vivo and ex vivo. We observed that the deletion of Mrgprd accelerated the transmission of charcoal through the mouse GI tract. But Mrgprd deficiency did not affect the mean amplitudes and frequencies of spontaneous contractions in ileum ex vivo. Colonic motor complexes in the proximal and the distal colon were recorded from wild-type and Mrgprd^-/- mice, but their control frequencies were not different. Moreover, in wild-type mice, systemic administration of an MrgprD agonist, either β-alanine or alamandine, delayed GI transit in vivo and suppressed spontaneous contractions in the ileum and colonic motor complexes in the colon ex vivo. Our results suggest that MrgprD and its agonist are involved in the modulation of GI motility in mice.