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- Title
Attenuation of signal flow from P2Y[sub 6] receptor by protein kinase C-α in SK-N-BE(2)C human neuroblastoma cells.
- Authors
Lee, Hyun; Choi, Bo-Hwa; Suh, Byung-Chang; Lee, Sun-Kyong; Kim, Kyong-Tai
- Abstract
Abstract Extracellular nucleotides exert a variety of biological actions through several kinds of P2 receptors in many tissues and cell types. We found that treatment with nucleotides increases intracellular Ca[sup 2+] concentration ([Ca[sup 2+]][sub i]) in SK-N-BE(2)C human neuroblastoma cells with a following order of potency: UDP > UTP > ADP >> ATP. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that specific mRNAs coding for human P2Y[sub 1], P2Y[sub 4], and P2Y[sub 6] receptors were expressed in the cells, but Northern blot analysis revealed that P2Y[sub 6] receptors were the predominant type. Activation of protein kinase C-α by treatment with 1 µ m phorbol 12-myristate 13-acetate dramatically inhibited both the UDP-induced [Ca[sup 2+]][sub i] rise and inositol 1,4,5-trisphosphate (IP[sub 3]) generation, whereas incubation with pertussis toxin had little effect on the responses. The UDP-induced [Ca[sup 2+]][sub i] rise and IP[sub 3] production were maintained up to 30 min after stimulation, while bradykinin-induced responses rapidly decreased to the basal level within 5 min of stimulation. Pretreatment of cells with the maximal effective concentration of UDP reduced the subsequent carbachol- or bradykinin-induced [Ca[sup 2+]][sub i] rise without inhibition of IP[sub 3] generation. Neuronal differentiation of the cells by treatment with retinoic acid for 7 days did not change the expression level of P2Y[sub 6] receptors. Taken together, the data indicate that P2Y[sub 6] receptors highly responsive to diphosphonucleotide UDP are endogenously expressed in the human neuroblastoma SK-N-BE(2)C cells and that they are involved in the modulation of other phospholipase C-coupled receptor-mediated Ca[sup 2+] mobilization by depleting the IP[sub 3]-sensitive Ca[sup 2+] stores.
- Subjects
PROTEIN kinase C; NEUROBLASTOMA; POLYMERASE chain reaction
- Publication
Journal of Neurochemistry, 2003, Vol 85, Issue 4, p1043
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1046/j.1471-4159.2003.01761.x