Further studies of the mechanism(s) of polyunsaturated-fatty-acid-mediated increases in intracellular cAMP formation in N1E-115 neuroblastoma cells.
Following earlier observations that increasing the polyunsaturated fatty-acid (PUFA) content of N1E-115 neuroblastoma cells elevated basal and adenosine (Ado)-stimulated intracellular cyclic AMP (cAMP) formation, we carried out studies to determine the mechanism(s) by which PUFA exerted their modulatory effects. Basal increases in cAMP in the PUFA-enriched (PUFA+) cells were evident with short (60 sec) exposure to a phosphodiesterase inhibitor (Ro 20-1724), and increased to a maximum at 20 min; they were not observed in the absence of Ro 20-1724. Forskolin-stimulated cAMP formation in the presence of the Ro compound was 2- to 3-fold higher in the PUFA+ cells. Basal elevations in cAMP were reduced by approximately 70% by exposing the PUFA+ cells to Ado deaminase (ADA) or to an Ado antagonist, and were further increased by inhibiting ADA, which suggested that they could be producing endogenous Ado that activated stimulatory Ado receptors. However, this did not appear to involve PUFA-mediated stimulation of 5'-nucleotidase activity or inhibition of [3H]Ado uptake. Overall, the results of this study indicated that multiple mechanisms are involved in PUFA modulation of cAMP formation.
Murphy
M G
MG
Department of Physiology & Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
Byczko
Z
Z
D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D001481:Basal Metabolism / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D015649:Pentostatin / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D008041:Linoleic Acids; D011983:Receptors, Purinergic; D005576:Colforsin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D015649:Pentostatin; D004176:Dipyridamole; D019787:Linoleic Acid; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D000241:Adenosine