title: Characterization of signaling pathways coupled to melatonin receptors in gastrointestinal smooth muscle.
abstract: Melatonin, a close derivative of serotonin, is involved in physiological regulation of circadian rhythms. In the gastrointestinal (GI) system, melatonin exhibits endocrine, paracrine and autocrine actions and is implicated in the regulation of GI motility. However, it is not known whether melatonin can also act directly on GI smooth muscle cells. The aim of the present study was to determine the expression of melatonin receptors in smooth muscle and identify their signaling pathways. MT1, but not MT2 receptors are expressed in freshly dispersed and cultured gastric smooth muscle cells. Melatonin selectively activated Gq and stimulated phosphoinositide (PI) hydrolysis in freshly dispersed and cultured muscle cells. PI hydrolysis was blocked by the expression of Gq, but not Gi minigene in cultured muscle cells. Melatonin also caused rapid increase in cytosolic Ca(2+) as determined by epifluorescence microscopy in fura-2 loaded single smooth muscle cells, and induced rapid contraction. Melatonin-induced PI hydrolysis and contraction were blocked by a non-selective MT1/MT2 antagonist luzindole (1 μM), but not by a selective MT2 antagonist 4P-PDOT (100 nM), and by the PLC inhibitor U73122. MT2 selective agonist IIK7 (100 nM) had no effect on PI hydrolysis and contraction. We conclude that rabbit gastric smooth muscle cells express melatonin MT1 receptors coupled to Gq. Activation of these receptors causes stimulation of PI hydrolysis and increase in cytosolic Ca(2+), and elicits muscle contraction.
authors.affiliation: Department of Physiology and VCU Program in Enteric Neuromuscular Sciences (VPENS), Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Rashad
authors.initials: R
authors.lastname: Ahmed
authors.forename: Sunila
authors.initials: S
authors.lastname: Mahavadi
authors.forename: Othman
authors.initials: O
authors.lastname: Al-Shboul
authors.forename: Sayak
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: John R
authors.initials: JR
authors.lastname: Grider
authors.forename: Karnam S
authors.initials: KS
authors.lastname: Murthy
mesh_terms: D000818:Animals; D041981:Gastrointestinal Tract / Q000378:metabolism*; D054833:Isoindoles / Q000494:pharmacology; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011817:Rabbits; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C121417:IIK7; D054833:Isoindoles; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2
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