Neuropeptide Y modulates ATP-induced increases in internal calcium via the adenylate cyclase/protein kinase A system in a human neuroblastoma cell line.
The modulatory effects of neuropeptide Y (NPY) on ATP-induced increases in cytosolic free-calcium concentration ([Ca2+]i) were investigated in the CHP-234 human neuroblastoma cell line. Pretreatment of cells with 100 nM NPY potentiated the increase in [Ca2+]i evoked subsequently by 20 microM ATP, compared with initial application of ATP in a control experiment, whereas a similar pretreatment with 1 microM NPY attenuated the subsequent response to ATP. Both actions of NPY were completely blocked by H-89 [N-[2-((3-(4-bromo-phenyl)-2-propenyl)-amino)-ethyl]-5 isoquinoline sulphonamide dihydrochloride], a selective antagonist of protein kinase A. The effects of 100 nM NPY were mimicked by H-89, while forskolin and 8-Br-cAMP mimicked the effects of 1 microM NPY. Both basal and forskolin-stimulated cAMP levels were inhibited by 100 nM NPY and by 100 nM NPY(13-36), a selective agonist of the NPY Y2-receptor subtype. In contrast, at 1 microM such inhibition was not observed for either NPY or NPY(13-36). It is concluded that NPY has a biphasic modulatory effect on increases in [Ca2+]i produced by ATP, which probably involves the cAMP/protein kinase A cascade.
Soares Lemos
V
V
Université Louis Pasteur de Strasbourg, Laboratoire de Pharmacologie et Physiopathologie Cellulaires-CNRS URA600, Illkirch, France.
Bucher
B
B
Takeda
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000263:Adenylate Kinase / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology* / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009478:Neuropeptide Y; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000263:Adenylate Kinase; D002118:Calcium