Effects of L-arginine in rat adrenal cells: involvement of nitric oxide synthase.
The effects of L-arginine on corticosterone production, cGMP, and nitrite levels were examined in zona fasciculata adrenal cells. L-Arginine significantly decreased both basal and ACTH-stimulated corticosterone production. This effect was still evident when steroidogenesis was induced by 8-bromo-cAMP and 22(R)-hydroxycholesterol, but not in the presence of exogenously added pregnenolone. L-Arginine increased cGMP and nitrite levels,; these effects were blocked by the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl-ester. Transport of L-[3H]arginine was rapid, saturable, and monophasic, with an apparent Km of 163+/-14 microM and a maximum velocity of 53+/-6 pmol/min x 10(5) cells. The basic amino acids L-lysine and L-ornithine, but not D-arginine or the nitric oxide synthase inhibitors N(G)-nitro-L-arginine methyl-ester and N(G)-nitro-L-arginine, impaired L-arginine uptake. Taken together, these results suggest that steroidogenesis in zona fasciculata adrenal cells may be negatively modulated by L-arginine-derived nitric oxide.
Cymeryng
C B
CB
Departamento de Bioquímica, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina. CCYMERYN@fmed.uba.ar
Dada
L A
LA
Colonna
C
C
Mendez
C F
CF
Podestá
E J
EJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D003345:Corticosterone / Q000096:biosynthesis; D006152:Cyclic GMP / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000494:pharmacology; D008239:Lysine / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D009952:Ornithine / Q000494:pharmacology; D011284:Pregnenolone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; C003585:22-hydroxycholesterol; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011284:Pregnenolone; D000324:Adrenocorticotropic Hormone; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone