title: Mechanisms of the prostaglandin F2alpha-induced rise in [Ca2+]i in rat intrapulmonary arteries.
abstract: The mechanisms by which prostaglandin F(2alpha) (PGF(2alpha)) increases intracellular Ca2+ concentration [Ca2+]i in vascular smooth muscle remain unclear. We examined the role of store-, receptor- and voltage-operated Ca2+ influx pathways in rat intrapulmonary arteries (IPA) loaded with Fura PE-3. Low concentrations (0.01-1 microM) of PGF(2alpha) caused a transient followed by a plateau rise in [Ca2+]i. Both responses became maximal at 0.1 microM PGF(2alpha). At higher concentrations of PGF(2alpha), a further slower rise in [Ca2+]i was superimposed on the plateau. The [Ca2+]i response to 0.1 microM PGF(2alpha) was mimicked by the FP receptor agonist fluprostenol, whilst the effect of 10 microM PGF(2alpha) was mimicked by the TP receptor agonist U-46619. The plateau rise in [Ca2+]i in response to 0.1 microM PGF(2alpha) was insensitive to diltiazem, and was abolished in Ca2+-free physiological salt solution, and by pretreatment with La3+, 2-APB, thapsigargin or U-73122. The rises in [Ca2+]i in response to 10 microM PGF(2alpha) and 0.01 microM U-46619 were partially inhibited by diltiazem. The diltiazem-resistant components of both of these responses were inhibited by 2-APB and La3+ to an extent which was significantly less than that seen for the response to 0.1 microM PGF(2alpha), and were also much less sensitive to U-73122. The U-46619 response was also relatively insensitive to thapsigargin. When Ca2+ was replaced with Sr2+, the sustained increase in the Fura PE-3 signal to 0.1 microM PGF(2alpha) was abolished, whereas 10 microM PGF(2alpha) and 0.05 microM U-46619 still caused substantial increases. These results suggest that low concentrations of PGF(2alpha) act via FP receptors to cause IP3-dependent Ca2+ release and store operated Ca2+ entry (SOCE). U-46619 and 10-100 microM PGF(2alpha) cause a TP receptor-mediated Ca2+ influx involving both L-type Ca2+ channels and a receptor operated pathway, which differs from SOCE in its susceptibility to La3+, 2-APB and thapsigargin, does not require phospholipase C activation, and is Sr2+ permeable.
authors.affiliation: Department of Asthma, Allergy and Respiratory Science, New Hunt's House, Guy's Hospital Campus, King's College London, London SE1 1UL, UK. vladimir.snetkov@kcl.ac.uk
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Snetkov
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Knock
authors.forename: Lynne
authors.initials: L
authors.lastname: Baxter
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Thomas
authors.forename: Jeremy P T
authors.initials: JP
authors.lastname: Ward
authors.forename: Philip I
authors.initials: PI
authors.lastname: Aaronson
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000032:analysis* / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D017482:Receptors, Thromboxane / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001896:Boron Compounds; D020746:Calcium Channels, L-Type; D002317:Cardiovascular Agents; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D014662:Vasoconstrictor Agents; C034671:prostaglandin F2alpha receptor; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015544:Inositol 1,4,5-Trisphosphate; D015237:Dinoprost; C109986:2-aminoethoxydiphenyl borate; D010738:Type C Phospholipases; D004110:Diltiazem; D002118:Calcium