ATP-Dependent inhibition of Ca2+-activated K+ channels in vascular smooth muscle cells by neuropeptide Y.
Neuropeptide Y(NPY) inhibits Ca2+-activated K+ channels reversibly in vascular smooth muscle cells from the rat tail artery. NPY (200 microM) had no effect in the absence of intracellular adenosine 5'-triphosphate (ATP) and when the metabolic poison cyanide-M-chlorophenyl hydrozone (10 microM) was included in the intracellular pipette solution. NPY was also not effective when ATP was substituted by the non-hydrolysable ATP analogue adenosine 5'-[beta gamma-methylene]-triphosphate (AMP-PCP). NPY inhibited Ca2+-activated K+ channel activity when ATP was replaced by adenosine 5'-O-(3-thiotriphosphate) (ATP [gamma-S]) and the inhibition was not readily reversed upon washing. Protein kinase inhibitor (1 microM), a specific inhibitor of adenosine 3', 5'-cyclic monophosphate-dependent protein kinase, had no significant effect on the inhibitory action of NPY. The effect of NPY on single-channel activity was inhibited by the tyrosine kinase inhibitor genistein (10 microM) but not by daidzein, an inactive analogue of genistein. These observations suggest that the inhibition by NPY of Ca2+-activated K+ channels is mediated by ATP-dependent phosphorylation. The inhibitory effect of NPY was antagonized by the tyrosine kinase inhibitor genistein.
Xiong
Z
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University of Ottawa, Heart Institute and Department of Pharmacology, 40 Ruskin Street, Ottawa K1Y 4E9, Canada.
Cheung
D W
DW
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D007529:Isoflavones; D009478:Neuropeptide Y; D015221:Potassium Channels; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium