Increase in cytosolic free Ca2+ in corticotropin-stimulated white adipocytes.
The mechanism of the adrenal corticotropin hormone (ACTH)-stimulated increase in cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in rat white adipocytes. ACTH at concentrations > 10 mU/ml caused a rapid and transient increase in [Ca2+]i followed by a small but sustained elevation of [Ca2+]i. A similar phenomenon was also induced by alpha-adrenergic or synthetic ACTH stimulation. The effect of norepinephrine (NE) plus ACTH on [Ca2+]i was nearly additive. Pertussis toxin completely blocked the ability of ACTH or NE to increase [Ca2+]i. NE but not ACTH caused a significant increase in inositol 1,4,5-trisphosphate levels. ACTH caused a rapid and transient accumulation of [3H]arachidonic acid (AA) and a marked loss of [3H]AA from phosphatidylinositol (PI) and phosphatidylcholine (PC) 10 s after stimulation. Neither a lipoxygenase inhibitor nor a dual inhibitor of cyclooxygenase and lipoxygenase blocked the increases in [Ca2+]i and the accumulation of [3H]AA in response to ACTH. On the other hand, either pertussis toxin or phospholipase A2 inhibitor drastically blocked both parameters in response to ACTH. These results indicate that ACTH stimulates AA release from PC and PI via the activation of phospholipase A2 coupled with pertussis toxin-sensitive GTP-binding protein(s), which leads to an increase in [Ca2+]i in rat white adipocytes.
Izawa
T
T
Department of Health and Sports Sciences, University of Electro-Communications, Tokyo, Japan.
Mochizuki
T
T
Komabayashi
T
T
Suda
K
K
Tsuboi
M
M
D000098:Acetophenones / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000098:Acetophenones; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; D016718:Arachidonic Acid; D015544:Inositol 1,4,5-Trisphosphate; D000324:Adrenocorticotropic Hormone; D037342:Pertussis Toxin; D010741:Phospholipases A; D054467:Phospholipases A2; D000262:Adenylyl Cyclases; C006821:4-bromophenacyl bromide; D002118:Calcium; D009638:Norepinephrine