ADRENOMEDULLIN AND CALCITONIN-GENE-RELATED PEPTIDE INTERACT WITH THE SAME RECEPTOR IN CULTURED HUMAN NEUROBLASTOMA SK-N-MC CELLS

被引:71
作者
ZIMMERMANN, U
FISCHER, JA
MUFF, R
机构
[1] UNIV ZURICH, DEPT ORTHOPED SURG, CALCIUM METAB RES LAB, CH-8008 ZURICH, SWITZERLAND
[2] UNIV ZURICH, DEPT MED, CALCIUM METAB RES LAB, CH-8008 ZURICH, SWITZERLAND
关键词
ADRENOMEDULLIN; AMYLIN; ANTAGONIST; CALCITONIN GENE-RELATED PEPTIDE; CAMP; RECEPTORS;
D O I
10.1016/0196-9781(94)00195-C
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inhibition of human [I-125]calcitonin gene-related peptide-I ([I-125]hCGRP-I) binding by human adrenomedullin (hADM), its N-terminal truncated fragments, CGRP and amylin, and cyclic AMP accumulation were examined in the human neuroblastoma cell line SK-N-MC. Binding of [I-125]hCGRP-I(125 pM) was inhibited by hCGRP-I, hADM(1-52), hADM(13-52), and human amylin with IC50 of 0.32 +/- 0.06, 2.11 +/- 0.26, 3.45 +/- 0.54, and 68.8 +/- 6.6 nM, respectively. hCGRP-I(8-37) and hADM(22-52), which lack the N-terminal ring structure, inhibited [I-125]hCGRP-I binding with IC50 of 2.35 +/- 0.45 and > 1000 nM. hCGRP-I, hADM(1-52), hADM(13-52) and human amylin stimulated cAMP accumulation with EC(50) of 0.40 +/- 0.05, 18.1 +/- 2.6, 51.3 +/- 9.0 and 925 +/- 159 nM, respectively. hCGRP-I(8-37) (100 nM) antagonized hCGRP-I and hADM(1-52) stimulated cAMP production with the same K-i of 16.6 +/- 1.2 and 16.8 +/- 1.1 nM. In conclusion, human ADM, which is more distantly related to CGRP than amylin, interacts more potently with the CGRP receptor in SK-N-MC cells than amylin. The N-terminal ring structure of hADM, unlike that of hCGRP, is essential for binding to the CGRP receptor. Coupling of hADM binding to cAMP stimulation is less efficient than for hCGRP-I and is reduced by deletion of the unique 12 amino acid sequence of hADM N-terminal to the ring structure.
引用
收藏
页码:421 / 424
页数:4
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