Pharmacologically distinct intracellular calcium pools regulate tonic and oscillatory responses in porcine thoracic duct.
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.
Moffatt
James D
JD
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. james.moffat@kcl.ac.uk
Cocks
Thomas M
TM
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*
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