title: The type 1 angiotensin-II receptor mediates intracellular calcium mobilization in rat luteal cells.
abstract: The intracellular cytosolic calcium concentration ([Ca]i) was determined in cultured rat luteal cells using the calcium-chelating dye fura-2 and microspectrofluorimetry. Angiotensin-II (Ang-II) induced a dose-dependent transient increase in [Ca]i (ED50, 9.0 +/- 6.5 nM). After the initial peak in [Ca]i, cytosolic calcium returned to a secondary elevated basal level that was dependent upon the presence of extracellular calcium. Pretreatment of rat luteal cells with Ang-II (100 nM) desensitized a subsequent response to a higher concentration (1 microM), but did not desensitize a prostaglandin F2 alpha (PGF2 alpha)-induced calcium flux. Although the peak increases in [Ca]i induced by Ang-II (1 microM) and PGF2 alpha (10 microM) were not significantly different, the plateau phase stimulated by PGF2 alpha was significantly higher (P < 0.05) than that stimulated by Ang-II (1 microM). Pretreatment of luteal cells with the type 2 Ang-II receptor antagonist PD 123319 (10 microM) did not inhibit calcium mobilization; however, Ang-II (1 microM)-induced calcium mobilization was dose dependently blocked by the type 1 Ang-II receptor antagonist Losartan (DuP 753). The ID50 for Losartan was 5.2 +/- 1.8 nM. Pretreatment of the luteal cells with the endoplasmic reticulum calcium ATPase inhibitor thapsigargin (1 microM) also blocked Ang-II-induced calcium mobilization. These data demonstrate the presence of the type 1 Ang-II receptor in rat luteal cells, through which Ang-II dose dependently mobilizes calcium from an intracellular source, probably the endoplasmic reticulum.
authors.affiliation: Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: J R
authors.initials: JR
authors.lastname: Pepperell
authors.forename: G
authors.initials: G
authors.lastname: Nemeth
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: F
authors.initials: F
authors.lastname: Naftolin
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003338:Corpus Luteum / Q000166:cytology / Q000378:metabolism*; D003470:Culture Media; D015237:Dinoprost / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D019808:Losartan; D009994:Osmolar Concentration; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011945:Receptors, Angiotensin / Q000502:physiology*; D013729:Terpenes / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D003470:Culture Media; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013729:Terpenes; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D019284:Thapsigargin; D015237:Dinoprost; D000251:Adenosine Triphosphatases; D019808:Losartan; D002118:Calcium