The prostaglandin E series modulates high-voltage-activated calcium channels probably through the EP3 receptor in rat paratracheal ganglia

The modulation of high-voltage-activated (HVA) Ca2+ channels by the prostag landin E series (PGE(1) and PGE(2)) was studied in the paratracheal ganglio n cells. Prostaglandin E-1, E-2, STA(2) (a stable analogue of thromboxane A (2)), 17-phenyl-trinor-PGE(2) (an EP1-selective agonist) and sulprostone (a n EP3-selective agonist) inhibited the HVA Ca2+ current (HVA I-Ca) dose-dep endently, and the rank order of potency to inhibit HVA Ca2+ channels was su lprostone>PGE(2), PGE(1)>STA(2)much greater than 17-phenyl-trinor-PGE(2). S C-51089 (10(-5) M), a selective EP1-receptor antagonist, showed no effect o n the PGE(1)- or PGE(2)-induced inhibition of the HVA I-Ca, thereby indicat ing that PGE(1)- and PGE(2)-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). PGE(1) and PGE(2) also inhibite d the remaining I-Ca in a saturating concentration of nifedipine, omega-con otoxin-GVIA and omega-conotoxin-MVIIC, suggesting that R-type Ca2+ channels are involved. The inhibitory effect of PGE(1) or sulprostone was prevented by pretreatment with pertussis toxin [islet activating protein (IAP)] or p horbol-12-myristate-13-acetate (PMA), and the protein kinase C (PKC) inhibi tor chelerythrine blocked the action of PMA. It was concluded that PGE, sel ectively reduces both N- and R-type Ca2+ currents by activating a G-protein probably through the EP3 receptor in paratracheal ganglion cells. (C) 2000 Published by Elsevier Science Ltd. All rights reserved.