The NANC relaxation of the human ileal longitudinal and circular muscles is inhibited by MRS 2179, a P2 purinoceptor antagonist

Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine

“…This result is consistent with results already published both in the circular and in the longitudinal muscle of the human small intestine where MRS2179, in combination with inhibitors of NO synthesis, totally abolishes EFS‐induced relaxation (Ref. and present study). From the pharmacological point of view, the IC 50 reported in this study for MRS2179 (0.55 μM) is in the same range of concentration to those reported in other studies both in the human colon (EFS‐induced IJP 1.2 μM and relaxation 0.9 μM, respectively) and in the small intestine EFS‐induced relaxation (about 3 μM) .…”

“…In the human jejunum, the fast response is probably ATP mediated, whereas the slow response is nitric oxide mediated . The nature of the receptors involved in the IJP of the human small intestine is unknown, although a previous report suggests that possibly P2Y 1 receptors (blocked by 2′‐deoxy‐N 6 ‐methyladenosine 3′,5′‐bisphosphate tetrasodium salt [MRS2179]) might be involved in mechanical relaxation induced by EFS both in the longitudinal and in the circular muscle of the human ileum . In the human colon, we have recently characterized the receptor involved in purinergic relaxation .…”

Unexpected Insensitivity of the Cholinergic Motor Responses to Morphine in the Human Small Intestine

“…In the current study, we were able to induce primary cholinergic contractions in the human small intestinal longitudinal muscle. EFS of nerves in this preparation (0.5 or 1 Hz) elicits a non-adrenergic, non-cholinergic inhibitory response that seems to be mediated by nitrergic and purinergic mechanisms, in a supra-additive manner [7] . We obtained cholinergic responses in the presence of the nitric oxide (NO) synthase blocker N G -nitro-L -arginine ( L -NOARG) plus the P 2Y receptor antagonist MRS 2179 at 0.5-and 5-Hz stimulation or in untreated preparations with 5-Hz stimulation and compared the sensitivity of these responses to morphine with that of the guinea pig small intestine.…”

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

“…Myocytes isolated from the longitudinal muscle of jejunum and ileum showed a slow transient increase in [Ca 2+ ] i in response to ATP and 2-MeSATP, suggesting P2Y receptor mediation [63]. The NANC relaxation of the human ileal longitudinal and circular muscle is inhibited by MRS2179, a selective P2Y 1 receptor antagonist [669]. Duodenal brush border intestinal alkaline phosphatase degrades ATP released from the epithelium and stimulates HCO 3 − secretion via P2Y receptor activation [483].…”