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 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.
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PGE2 Ca2+ PGE1 sulprostone phorbol-12-myristate-13-acetate PMA chelerythrine PMA PGE1 Ca2+ Prostaglandin E1, E2, STA2 thromboxane A2 17-phenyl-trinor-PGE2 sulprostone Ca2+ Ca2+ sulprostone PGE2 PGE1 STA2 17-phenyl-trinor-PGE2 Ca2+ SC-51089 PGE1 PGE2 PGE1 PGE2 Ca2+ prostaglandin E PGE1 nifedipine PGE1 PGE2 PGE1 nifedipine prostaglandin E calcium R-type Ca2+ channels pertussis toxin islet activating protein IAP protein kinase C PKC G-protein EP3 receptor high-voltage-activated (HVA) Ca2+ channels EP1 EP3 HVA Ca2+ channels EP1-receptor HVA Ca2+ channels EP3 receptor high-voltage-activated calcium channels EP3 receptor