Prostaglandin E2 induces Ca2+ release from ryanodine/caffeine-sensitive stores in bovine adrenal medullary cells via EP1-like receptors.
Prostaglandin E2 (PGE2) causes Ca2+ release from intracellular Ca2+ stores and stimulates phosphoinositide metabolism in bovine adrenal medullary cells. These results have been interpreted as PGE2 induces Ca2+ release from inositol trisphosphate (IP3)-sensitive stores. However, we have recently shown that pituitary adenylate cyclase-activating polypeptide (PACAP), bradykinin, and angiotensin II release Ca2+ from caffeine/ryanodine-sensitive stores, although they cause a concomitant increase of intracellular IP3. In light of these results, the mechanism of PGE2-induced Ca2+ release was investigated in the present study. PGE2 dose-dependently caused a transient but consistent Ca2+ release from internal Ca2+ stores. The PGE2-induced Ca2+ release was unaffected by cinnarizine, a blocker of IP3-induced Ca2+ release. By contrast, it was potently inhibited by prior application of caffeine and ryanodine. Although IP3 production in response to PGE2 was abolished by the phospholipase C inhibitor U-73122, Ca2+ release in response to PGE2 was unaffected by U-73122. The PGE2-induced Ca2+ release was unaffected by Rp-adenosine 3',5'-cyclic monophosphothioate, an inhibitor of protein kinase A, and forskolin, a cyclic AMP (cAMP)-elevating agent, did not cause Ca2+ release. The EP1 agonist 17-phenyl-trinorPGE2 and the EP1/EP3 agonist sulprostone mimicked the Ca(2+)-releasing effects of PGE2, whereas the EP2 agonist butaprost or the EP2/EP3 agonist misoprostol caused little or no Ca2+ release. The EP1 antagonist SC-51322 significantly suppressed the Ca2+ release response induced by PGE2, whereas the EP4 antagonist AH-23828B had little effect. These results suggest that PGE2, acting on EP1-like receptors, induces Ca2+ release from ryanodine/caffeine-sensitive stores through a mechanism independent of IP3 and cAMP and that PGE2 may share the same mechanism with PACAP and the other peptide ligands in causing Ca2+ release in bovine adrenal medullary cells.
Shibuya
I
I
Department of Physiology, University of Occupational and Environmental Health School of Medicine, Kitakyushu, Japan.
Tanaka
K
K
Uezono
Y
Y
Ueta
Y
Y
Toyohira
Y
Y
Yanagihara
N
N
Izumi
F
F
Yamashita
H
H
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012433:Ryanodine / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
C092396:17-phenyltrinorprostaglandin E2; D007295:Inositol Phosphates; D018078:Receptors, Prostaglandin E; D012433:Ryanodine; D002110:Caffeine; C016767:sulprostone; D017868:Cyclic AMP-Dependent Protein Kinases; D010738:Type C Phospholipases; D015232:Dinoprostone; D002118:Calcium