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The anatomical arrangement of the LOS includes semicircular clasp fibres adjacent to the lesser gastric curvature and sling fibres following the greater gastric curvature. Such anatomical arrangement together with an asymmetric intrinsic innervation and distinct proportion of neurotransmitters in both regions produces an asymmetric pressure profile. The LOS tone is myogenic in origin and depends on smooth muscle properties that lead to opening of L\u2010type Ca<jats:sup>2+<\/jats:sup>channels; however it can be modulated by enteric motor neurons, the parasympathetic and sympathetic extrinsic nervous system and several neurohumoral substances. Nitric oxide synthesized by neuronal NOS is the main inhibitory neurotransmitter involved in LOS relaxation. Different putative neurotransmitters have been proposed to play a role together with NO. So far, only ATP or related purines have shown to be co\u2010transmitters with NO. Acetylcholine and tachykinins are involved in the LOS contraction acting through acetylcholine M<jats:sub>3<\/jats:sub>and tachykinin NK<jats:sub>2<\/jats:sub>receptors. Nitric oxide can also be involved in the regulation of LOS contraction. The understanding of the mechanisms that originate and modulate LOS tone, relaxation and contraction and the characterization of neurotransmitters and receptors involved in LOS function are important to develop new pharmacological tools to treat primary oesophageal motor disorders and gastro\u2010oesophageal reflux disease.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2008)<jats:bold>153<\/jats:bold>, 858\u2013869; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707572\">10.1038\/sj.bjp.0707572<\/jats:ext-link>; published online 12 November 2007<\/jats:p>","DOI":"10.1038\/sj.bjp.0707572","type":"journal-article","created":{"date-parts":[[2007,11,12]],"date-time":"2007-11-12T11:07:56Z","timestamp":1194865676000},"page":"858-869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Regulation of basal tone, relaxation and contraction of the lower oesophageal sphincter. 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