AMYLIN INCREASES CYCLIC-AMP FORMATION IN L6 MYOCYTES THROUGH CALCITONIN GENE-RELATED PEPTIDE RECEPTORS

被引:47
|
作者
ZHU, GC
DUDLEY, DT
SALTIEL, AR
机构
[1] WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES DIV,DEPT SIGNAL TRANSDUCT,2800 PLYMOUTH RD,ANN ARBOR,MI 48106
[2] UNIV MICHIGAN,SCH MED,DEPT PHYSIOL,ANN ARBOR,MI 48109
关键词
D O I
10.1016/0006-291X(91)91855-7
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
The cellular function of amylin is investigated in L6 myocytes, a rat skeletal muscle cell line. Both rat amylin and human amylin-amide acutely cause a dose-dependent increase in cyclic AMP formation in L6 myocytes. 100 nM rat amylin stimulates intracellular cyclic AMP concentrations 12-fold, whereas human amylin-amide at this concentration causes only a 2-fold increase. Up to 10 mM human amylin has no effect on cyclic AMP levels. Rat calcitonin gene-related peptide (CGRP) is more potent than amylin, causing a 60-fold increase over basal at 1 nM, with an EC50 value of 0.2 nM. The CGRP receptor antagonist, human CGRP8-37 (hCGRP8-37), completely blocks the stimulatory effect of both rat amylin and human amylin-amide on cyclic AMP production. [125I]CGRP binds specifically to a membrane fraction prepared from L6 myocytes with a Kd = 2.1 nM and Bmax = 144 fmol/mg protein. The antagonist peptide displaces [125I]CGRP with a Ki of 0.9 nM, while rat amylin also displaces [125I]CGRP with a Ki of 91 nM. Specific binding of [125I]CGRP to plasma membranes of rat liver and brain is also displaced by rat amylin with Ki values of 35 nM and 37 nM, respectively. In contrast, specific binding of [125I]amylin to numerous cells and tissues, under similar conditions, can not be demonstrated. These results suggest that the cellular effects and physiological actions of amylin may be mediated through receptors for CGRP. © 1991.
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页码:771 / 776
页数:6
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