Abstract
Colonic motor activity is important for the formation and propulsion of feces. The production of prostaglandins (PGs) in colonic tissue is considered to play a critical role in the generation and regulation of colonic motility. In this study, we investigated the inhibitory effects of PGE2 and selective agonists of four EP receptors on the spontaneous phasic contractions, called ‘giant contractions’ (GCs), of mucosa-free circular smooth muscle strips from the rat middle colon. Neural blockade with tetrodotoxin (TTX) increased the frequency and amplitude of the GCs by about twofold. However, inhibiting PG production with piroxicam reduced the GC frequency in the presence of TTX, but did not affect the GC amplitude. In the presence of both TTX and piroxicam, exogenous PGE2 and each EP receptor agonist were cumulatively added to the tissue bath. In this setting, PGE2, the EP2 agonist ONO-AE1-259, and the EP4 agonist ONO-AE1-329, but not the EP1 agonist ONO-AE-DI-004 or the EP3 agonist ONO-AE-248, concentration-dependently reduced the GC frequency and amplitude. The PGE2-induced inhibition of GC frequency and amplitude was inhibited by the EP4 antagonist ONO-AE3-208, but not by the EP1/2 antagonist AH6809. Immunohistochemistry revealed the EP2 and EP4 receptors were localized in perinuclear sites in circular smooth muscle cells. EP2 immunoreactivity was also located in GFAP-immunoreactive enteroglia, whereas EP4 immunoreactivity was also located in HU (embryonic lethal, abnormal vision [ELAV] protein; a marker of all myenteric neurons)-immunoreactive myenteric nerve cell bodies. These results suggest that the PGs produced in the colonic tissue inhibit the GC frequency and amplitude of circular muscle in the rat middle colon, and is mediated by EP4 receptors expressed in the smooth muscle cells.
Highlights
Colonic motor activity must be precisely regulated to form and propel feces adequately
E P2 immunoreactivity was located in glial fibrillary acidic protein (GFAP)-immunoreactive enteroglia, whereas EP4 immunoreactivity was located in HU-immunoreactive myenteric nerve cell bodies. These results suggest that the PGs produced in the colonic tissue inhibit the giant concentrations (GCs) frequency and amplitude of circular muscle in the rat middle colon, and is mediated by EP4 receptors expressed in the smooth muscle cells
We reported that in rat middle colonic longitudinal muscle (LM) strips, PG production is required for the generation of spontaneous GCs because the cyclooxygenase (COX) inhibitor, piroxicam, completely inhibits GCs [18]
Summary
Colonic motor activity must be precisely regulated to form and propel feces adequately. To perform these functions, the colonic wall displays complex and varied spatiotemporal characteristics of motility. In a variety of species, including dogs, humans, and rats, three distinct types of contractions have been characterized by in vivo recordings: rhythmic phasic contractions (RPCs), giant. Isolated circular muscle (CM) strips from the human and dog colon only generate RPCs and TCs in vitro, giant concentrations (GCs) similar to GMCs have been recorded in isolated rat CM strips from the middle colon [3]. In the 1960s, before the PG receptors were identified, it was reported that PGE2 enhances the motility of longitudinal muscle (LM) [6–8] but reduces the motility of CM [7, 8]. The E P3 receptor is coupled to G i and reduces intracellular cAMP levels [17]
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