INCREASE IN CYTOSOLIC-FREE CA2-STIMULATED WHITE ADIPOCYTES( IN CORTICOTROPIN)

The mechanism of the adrenal corticotropin hormone (ACTH)-stimulated i ncrease in cytosolic free Ca2+ concentration ([Ca2+](i)) was investiga ted in rat white adipocytes. ACTH at concentrations > 10 mU/ml caused a rapid and transient increase in [Ca2+](i) followed by a small but su stained elevation of [Ca2+](i). A similar phenomenon was also induced by alpha-adrenergic or synthetic ACTH stimulation. The effect of norep inephrine (NE) plus ACTH on [Ca2+](i) was nearly additive. Pertussis t oxin 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-tri sphosphate levels. ACTH caused a rapid and transient accumulation of [ H-3]arachidonic acid (AA) and a marked loss of [H-3]AA from phosphatid ylinositol (PI) and phosphatidylcholine (PC) 10 s after stimulation. N either a lipoxygenase inhibitor nor a dual inhibitor of cyclooxygenase and lipoxygenase blocked the increases in [Ca2+](i) and the accumulat ion of [H-3]AA in response to ACTH. On the other hand, either pertussi s toxin or phospholipase A(2) inhibitor drastically blocked both param eters in response to ACTH. These results indicate that ACTH stimulates AA release from PC and PI via the activation of phospholipase A(2) co upled with pertussis toxin-sensitive GTP-binding protein(s), which lea ds to an increase in [Ca2+](i) in rat white adipocytes.