Department of Pharmacology (I), Jikei University School of Medicine, 3 - 25 - 8, Nishi-Shinbashi, Minato-ku, Tokyo 105 - 8461, Japan
Abstract: Both extracellular adenosine 5'-triphosphate (ATP) and uridine 5'-triphosphate (UTP) induced corticoid production (steroidogenesis) concentration-dependently in bovine adrenocortical cells (BA cells). Pertussis toxin (PTX, approx. 2 ƒÊg/ml) partially inhibited (approx. 55% inhibition) extracellular ATP (100 ƒÊM)-induced steroidogenesis in BA cells. However, PTX did not inhibit extracellular UTP (100 ƒÊM)-induced steroidogenesis. Both ATP- and UTP-induced steroidogeneses were significantly inhibited by suramin (50 - 200 ƒÊM). These effects were inhibited significantly by reactive blue-2 (more than 100 ƒÊM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (more than 100 ƒÊM). Both nucleotides (1 - 100 ƒÊM) induced inositol phosphates accumulation and intracellular Ca2+ mobilization, but PTX did not inhibit them. The RT-PCR procedure identified only P2Y2-receptor mRNA in BA cells. These results suggest that extracellular ATP induces steroidogenesis via a unique P2 receptor linked to PTX-sensitive guanine nucleotide-binding protein (G-protein), while extracellular UTP induces steroidogenesis via P2 receptor linked to PTX-insensitive G-protein. Thus, it was concluded that at least two different P2Y-like receptors linking to steroidogenesis exist in BA cells.
Keywords: Steroidogenesis, P2 receptor, Bovine adrenocortical cell, ATP, UTP