title: The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia.
abstract: The modulation of high-voltage-activated (HVA) Ca2+ channels by the prostaglandin E series (PGE1 and PGE2) was studied in the paratracheal ganglion cells. Prostaglandin E1, E2, STA2 (a stable analogue of thromboxane A2), 17-phenyl-trinor-PGE2 (an EP1-selective agonist) and sulprostone (an EP3-selective agonist) inhibited the HVA Ca2+ current (HVA ICa) dose-dependently, and the rank order of potency to inhibit HVA Ca2+ channels was sulprostone>PGE2, PGE1>STA2>>17-phenyl-trinor-PGE2. SC-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect on the PGE1- or PGE2-induced inhibition of the HVA ICa, thereby indicating that PGE1- and PGE2-induced inhibition of the HVA Ca2+ channels is possibly mediated by the EP3 receptor. The PGE1-sensitive component of the current was markedly reduced in the presence of omega-conotoxin-GVIA (3x10(-6) M), but not with nifedipine (3x10(-6) M). PGE1 and PGE2 also inhibited the remaining ICa in a saturating concentration of nifedipine, omega-conotoxin-GVIA and omega-conotoxin-MVIIC, suggesting that R-type Ca2+ channels are involved. The inhibitory effect of PGE1 or sulprostone was prevented by pretreatment with pertussis toxin [islet activating protein (IAP)] or phorbol-12-myristate-13-acetate (PMA), and the protein kinase C (PKC) inhibitor chelerythrine blocked the action of PMA. It was concluded that PGE1 selectively reduces both N- and R-type Ca2+ currents by activating a G-protein probably through the EP3 receptor in paratracheal ganglion cells.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. yushi@med.kyushu-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: Y
authors.initials: Y
authors.lastname: Murai
authors.forename: H
authors.initials: H
authors.lastname: Ishibashi
authors.forename: H
authors.initials: H
authors.lastname: Onoue
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D020908:Calcium Channels, R-Type / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D004789:Enzyme Activation; D005724:Ganglia / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D011458:Prostaglandins E / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D020864:Calcium Channels, N-Type; D020908:Calcium Channels, R-Type; D011458:Prostaglandins E; C545649:Ptger3 protein, rat; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D010566:Virulence Factors, Bordetella; C016767:sulprostone; D037342:Pertussis Toxin; D011493:Protein Kinase C; D000527:Alprostadil; D015232:Dinoprostone