Angiotensin II-activated Ca2+ entry-induced release of Ca2+ from intracellular stores in rat portal vein myocytes.
1. The action of angiotensin II (AII) was studied in single myocytes from rat portal vein in which the cytoplasmic Ca2+ concentration was estimated by emission from dyes Fura-2 or Indo-1 and the Ca2+ channel current was measured with the whole-cell mode of the patch-clamp technique. 2. Most of the AII-evoked increases in [Ca2+]i were reduced by about 60% after pretreatment with ryanodine and caffeine to deplete intracellular Ca2+ stores. However, in some cells the AII-induced Ca2+ responses were of small amplitude and resembled those obtained in the presence of ryanodine and caffeine. Both types of Ca2+ responses induced by AII were selectively inhibited by losartan, suggesting that the AII effects resulted from activation of the angiotensin AT1 receptors. 3. The concentration-response curve to AII had an EC50 value close to 1 nM for the increase in [Ca2+]i obtained after depletion of intracellular Ca2+ stores. This value was increased to around 18 nM in experiments where the intracellular Ca2+ stores were not depleted. 4. AII-evoked Ca2+ responses were abolished in the absence of external Ca2+ and in the presence of 1 microM oxodipine to block L-type Ca2+ channels. 5. Intracellular applications of the InsP3 receptor antagonist, heparin or an anti-PdtIns antibody did not modify AII-induced Ca2+ responses. 6. Our results show that AII releases Ca2+ from intracellular stores without involving InsP3 but through a Ca2+ release mechanism activated by Ca2+ influx through L-type Ca2+ channels.
Morel
J L
JL
Laboratoire de Physiologie Cellulaire et Pharmacologie Moléculaire, URA CNRS 1489, Université de Bordeaux II, France.
Macrez-Leprêtre
N
N
Mironneau
J
J
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000276:immunology; D011169:Portal Vein / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology
D000906:Antibodies; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D010716:Phosphatidylinositols; D018160:Receptors, Cytoplasmic and Nuclear; D000804:Angiotensin II; D006493:Heparin; D002118:Calcium