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Neuropeptide Y Signaling in Altered Catecholamine Synthesis during Intermittent Hypoxia
Author(s) -
Kumar Ganesh K,
Raghuraman Gayatri,
Prabhakar Nanduri R
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.899.12
Subject(s) - neuropeptide y receptor , tyrosine hydroxylase , medicine , endocrinology , adrenal medulla , catecholamine , chemistry , tyrosine 3 monooxygenase , phosphorylation , protein kinase a , receptor , neuropeptide , dopamine , biology , biochemistry
Intermittent hypoxia (IH) increases catecholamine (CA) levels in the adrenal medulla. In this study we examined whether the IH‐induced increase in CA is due to alterations in tyrosine hydroxylase (TH), the rate‐limiting enzyme in CA biosynthesis. Rats and mice were exposed to IH (15s of 5% O 2 ; 5 min of 21% O 2 ; 8 h per day for 10 days) or normoxia (21% O 2 ) and adrenal medullae were harvested for analyses. IH increased TH activity and TH phosphorylation at ser‐40 (~ 3 fold), without altering TH protein levels. In addition to CA, adrenal medulla also expresses neuropeptide Y (NPY) which is known to modulate TH activity via activation of G‐protein coupled Y1 receptors (Y1R). IH markedly up regulated the expression of NPY levels, Y1R expression, cAMP levels and protein kinase A (PKA) activity. The contribution of NPY in IH‐induced TH activation was examined using 4‐phenyl‐3‐butenoic acid (PBA), an inhibitor of bioactive NPY synthesis. PBA treatment prevented IH‐induced increases in NPY levels, TH activity, TH phosphorylation (ser‐40) and CA levels. Furthermore IH‐induced increases in TH phosphorylation and activity and up regulation of PKA activity were absent in Y1R −/− but not in Y2R −/− mice. Taken together, these results suggest that NPY‐Y1R‐PKA signaling mediates IH‐induced increase in CA synthesis in the adrenal medulla (supported by grants from NIH HL‐89616 and HL‐90554).