title: Pharmacologically distinct intracellular calcium pools regulate tonic and oscillatory responses in porcine thoracic duct.
abstract: The present study investigated the mechanisms by which the thromboxane A2 mimetic U46619 can elicit phasic and tonic contractions in the pig thoracic duct, whereas other agonists like 5-hydroxytryptamine (5-HT) produce tonic contractions only. Tonic contractions in response to either agonist were abolished by the l-type voltage-operated calcium channel (VOCC) inhibitor nifedipine, the store-operated calcium channel inhibitor SKF 96365, the calcium-sensitive chloride channel (ClCa) inhibitor niflumic acid, and by removal of extracellular Cl-. Superimposed phasic responses to U46619 were abolished by only nifedipine. Inhibitors of K+ channels did not prevent phasic contractions to U46619. The IP3 receptor antagonist 2-APB attenuated tonic contractions only, whereas ryanodine and removal of extracellular Na+ selectively abolished phasic contractions to U46619. Therefore, selective initiation of phasic contractions by U46619 appears to depend on intracellular Ca2+ from a ryanodine-sensitive store that causes depolarization via Na+/Ca2+ exchange, whereas tonic contractions to U46619 and 5-HT are mediated primarily by release of IP3-mobilized intracellular Ca2+ that subsequently causes ClCa opening, membrane depolarization, and Ca2+ entry via l-type VOCC.
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. james.moffat@kcl.ac.uk
authors.forename: James D
authors.initials: JD
authors.lastname: Moffatt
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Cocks
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004347:Drug Interactions; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D002120:Calcium Channel Agonists; D015220:Calcium Channels; D014662:Vasoconstrictor Agents; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D002118:Calcium