{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:28:46Z","timestamp":1781836126138,"version":"3.54.5"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T00:00:00Z","timestamp":1361404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Vasoactive intestinal polypeptide (VIP)\u2010ergic neuromuscular transmission (NMT) was examined in the internal anal sphincter of wild\u2010type mice and compared with that of<jats:italic>VIP<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Relaxation and hyperpolarization during brief trains of electrical field stimulation (EFS; 4\u00a0s) were mediated by purinergic and nitrergic NMT.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>During longer stimulus trains, a non\u2010purinergic, non\u2010nitrergic (NNNP) relaxation and hyperpolarization slowly developed and persisted for several minutes beyond the end of the stimulus train.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>The NNNP NMT was abolished by VIP receptor antagonists, absent in the<jats:italic>VIP<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mouse internal anal sphincter and mimicked by exogenous VIP.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>These data suggest that NNNP NMT gives rise to ultraslow relaxation and hyperpolarization that is mediated by VIP.<jats:italic>In vivo<\/jats:italic>, this pathway may be activated with larger rectal distensions, leading to a more prolonged anal relaxation.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold>There is evidence that vasoactive intestinal polypeptide (VIP) participates in inhibitory neuromuscular transmission (NMT) in the internal anal sphincter (IAS). However, specific details concerning VIP\u2010ergic NMT are limited, largely because of difficulties in selectively blocking other inhibitory neural pathways. The present study used the selective P2Y<jats:sub>1<\/jats:sub>receptor antagonist MRS2500 (1\u00a0\u03bc<jats:sc>m<\/jats:sc>) and the nitric oxide synthase inhibitor<jats:italic>N<\/jats:italic><jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine (<jats:sc>l<\/jats:sc>\u2010NNA; 100\u00a0\u03bc<jats:sc>m<\/jats:sc>) to block purinergic and nitrergic NMT to characterize non\u2010purinergic, non\u2010nitrergic (NNNP) inhibitory NMT and the role of VIP in this response. Nerves were stimulated with electrical field stimulation (0.1\u201320\u00a0Hz, 4\u201360\u00a0s) and the associated changes in contractile and electrical activity measured in non\u2010adrenergic, non\u2010cholinergic conditions in the IAS of wild\u2010type and<jats:italic>VIP<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice. Electrical field stimulation gave rise to frequency\u2010dependent relaxation and hyperpolarization that was blocked by tetrodotoxin. Responses during brief trains of stimuli (4\u00a0s) were mediated by purinergic and nitrergic NMT. During longer stimulus trains, an NNNP relaxation and hyperpolarization developed slowly and persisted for several minutes beyond the end of the stimulus train. The NNNP NMT was abolished by VIP6\u201328 (30\u00a0\u03bc<jats:sc>m<\/jats:sc>), absent in the<jats:italic>VIP<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mouse and mimicked by exogenous VIP (1\u2013100\u00a0n<jats:sc>m<\/jats:sc>). Immunoreactivity for VIP was co\u2010localized with neuronal nitric oxide synthase in varicose intramuscular fibres but was not detected in the<jats:italic>VIP<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mouse IAS. In conclusion, this study identified an ultraslow component of inhibitory NMT in the IAS mediated by VIP.<jats:italic>In vivo<\/jats:italic>, this pathway may be activated with larger rectal distensions, leading to a more prolonged period of anal relaxation.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.247684","type":"journal-article","created":{"date-parts":[[2013,1,22]],"date-time":"2013-01-22T02:21:12Z","timestamp":1358821272000},"page":"1489-1506","source":"Crossref","is-referenced-by-count":29,"title":["Functional role of vasoactive intestinal polypeptide in inhibitory motor innervation in the mouse internal anal sphincter"],"prefix":"10.1113","volume":"591","author":[{"given":"K. D.","family":"Keef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. N.","family":"Saxton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. A.","family":"McDowall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. E.","family":"Kaminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"Duffy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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