Activation of extracellular signal regulated protein kinase by neuropeptide Y and pancreatic polypeptide in CHO cells expressing the NPY Y(1), Y(2), Y(4) and Y(5) receptor subtypes.
Neuropeptide Y (NPY), 36-amino acid amidated peptide expressed in central and peripheral neurons, regulates a variety of physiological activities, including food intake, energy expenditure, vasoconstriction, anxiolysis, nociception and ethanol consumption. NPY binds to a family of G-protein coupled receptors whose activation results in inhibition of adenylyl cyclase activity. To more fully characterize the signal transduction pathways utilized by the NPY receptor subtypes, the pathways leading to phosphorylation of the extracellular signal regulated protein kinases 1 and 2 (ERK) have been compared in CHO cells expressing each of the four cloned human NPY receptor subtypes, Y(1), Y(2), Y(4) and Y(5). NPY Y(1), Y(2), Y(4) and Y(5) receptor-mediated ERK phosphorylation was blocked by pertussis toxin (PTX) exposure, indicating that all four receptors are coupled to inhibitory G(i/o) proteins. Exposure to the protein kinase C (PKC) inhibitor GF109203X diminished Y(1), Y(2) and Y(4) receptor-mediated ERK phosphorylation but completely blocked Y(5) receptor-mediated ERK phosphorylation. Additionally, Y(5) receptor-mediated ERK phosphorylation was inhibited by the phosphatidylinositol 3-kinase inhibitors LY294002 and wortmannin to a greater extent than was Y(1)-mediated ERK phosphorylation. These results demonstrate that in CHO cells, the Y(5) receptor and the Y(1), Y(2) and Y(4) receptors utilize different pathways to activate ERK.
Mullins
Deborra E
DE
Department of Central Nervous System and Cardiovascular Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. deborra.mullins@spcorp.com
Zhang
Xiaoping
X
Hawes
Brian E
BE
D037361:Adenylate Cyclase Toxin; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002867:Chromones / Q000494:pharmacology; D003001:Cloning, Molecular; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology*; D010191:Pancreatic Polypeptide / Q000494:pharmacology*; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017476:Receptors, Neuropeptide Y / Q000145:classification* / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000077191:Wortmannin
D037361:Adenylate Cyclase Toxin; D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D009025:Morpholines; D009478:Neuropeptide Y; D020033:Protein Isoforms; D017476:Receptors, Neuropeptide Y; D010566:Virulence Factors, Bordetella; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D010191:Pancreatic Polypeptide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D020928:Mitogen-Activated Protein Kinases; C070515:bisindolylmaleimide I; D000077191:Wortmannin