DYNORPHIN BINDS TO NEUROPEPTIDE-Y AND PEPTIDE YY RECEPTORS IN HUMAN NEUROBLASTOMA CELL-LINES

被引:7
|
作者
MIURA, M
INUI, A
SANO, K
UENO, N
TERANISHI, A
HIROSUE, Y
NAKAJIMA, M
OKITA, M
TOGAMI, J
KOSHIYA, K
BABA, S
KASUGA, M
机构
[1] KOBE UNIV, SCH MED, DEPT INTERNAL MED 2, DEPT PEDIAT, CHUO KU, KOBE 650, JAPAN
[2] YAMANOUCHI PHARMACEUT CO LTD, INST DRUG DISCOVERY RES, TSUKUBA, IBARAKI 305, JAPAN
[3] HYOGO INST CLIN DIS, AKASHI, HYOGO 673, JAPAN
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1994年 / 267卷 / 05期
关键词
CORTICOTROPIN-RELEASING FACTOR; TRANS-3,4-DICHLORO-N-METHYL-N-[2-(1-PYRROLIDINYL)-CYCLOHEXYL] BENZENEACETAMIDE METHANE-SULFONATE HYDRATE; LUTEINIZING HORMONE-RELEASING HORMONE;
D O I
10.1152/ajpendo.1994.267.5.E702
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The modulation of neuropeptide Y (NPY) and peptide YY (PYY) receptors by dynorphin, luteinizing hormone-releasing hormone (LHRH), corticotropin-releasing factor (CRF), and cholecystokinin octapeptide has been studied in human neuroblastoma cell lines SK-N-MC and SMS-MSN, which express Y-1 and Y-2 receptors for NPY/PYY. Dynorphin A and LHRH inhibited the binding of NPY/PYY to SK-N-MC cell membranes at concentrations ranging from 10(-7) to 10(-5) M, whereas dynorphin A and CRF were effective in SMS-MSN cells. The inhibitory effect of dynorphin A on NPY/PYY binding was observed in the presence of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, as well as H-7 and H-8, novel inhibitors of protein kinases C and A, However, U-50488, the most potent kappa-selective compound did not mimic the dynorphin action. Dynorphin A showed neither effect on the dissociation of NPY/PYY from their receptors nor inhibition on the basal as well as forskolinstimulated adenosine 3',5'-cyclic monophosphate response. These results indicate that the interaction of dynorphin A with Y-1 and Y-2 receptors is not mediated by changes in receptor-G protein interaction, receptor phosphorylation, and allosteric binding to NPY/PYY receptors but that dynorphin A binds to NPY/PYY receptors at high concentrations, probably in an antagonistic manner.
引用
收藏
页码:E702 / E709
页数:8
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