Calcium mobilization and its desensitization induced by endothelins and sarafotoxin in human astrocytoma cells (1321N1): comparison of histamine-induced calcium mobilization.
Intracellular free Ca2+ concentration ([Ca2+]i) was monitored in monolayer of 1321 N1 astrocytoma cells by using a fluorescent Ca2+ indicator fura-2. Endothelin-1 (ET-1), endothelin-2 (ET-2), and sarafotoxin Sb6 (SRTX) increased [Ca2+]i from 56 +/- 6 nM to 360 +/- 82, 120 +/- 51, 143 +/- 29 nM, respectively, immediately after their addition to the perfusate with maximum response of more than 0.1 microM of peptides. Endothelin-3 (less than 1 microM) did not affect [Ca2+]i. The increase in [Ca2+]i in response to either ET-1, ET-2, or SRTX could be almost completely inhibited by pretreating cells with ET-1 or ET-2. The homologous desensitization of [Ca2+]i induced by ETs and SRTX is in good agreement with their affinity toward an ETA receptors. The responses in [Ca2+]i by ETs and SRTX were not affected in the desensitized state induced by the pretreatment of histamine in the presence of extracellular Ca2+. However, the response in [Ca2+]i by ETs and SRTX were reduced in the desensitized state induced by pretreatment of histamine in the absence of extracellular Ca2+. These results indicate that depletion of the intracellular Ca2+ stores is responsible for the heterologous desensitization between ETs and histamine.
Yanai
K
K
Department of Pharmacology I, Tohoku University School of Medicine, Sendai, Japan.
Maeyama
K
K
Nakahata
N
N
Nakanishi
H
H
Watanabe
T
T
D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007457:Iodine Radioisotopes; D014407:Tumor Cells, Cultured; D014757:Viper Venoms / Q000494:pharmacology*
D016232:Endothelins; D007457:Iodine Radioisotopes; D014757:Viper Venoms; C057354:sarafotoxins s6; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium