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alpha(1)-adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells.

Abstract：

:We have compared the coupling of human alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenoceptors (expressed at approximately 2000 fmol/mg protein in Chinese hamster ovary cells) to cellular growth promotion (as assessed by [(3)H]thymidine incorporation) and related signaling mechanisms. Maximum elevation of intracellular Ca(2+) by the three subtypes occurred with the rank order alpha(1A) (1691 nM) > alpha(1D) (1215 nM) > alpha(1B) (360 nM). In contrast, activation of the ERK, JNK, and p38 forms of mitogen-activated protein kinases occurred with the rank order alpha(1D) > alpha(1A) > alpha(1B). alpha(1A)-Adrenoceptor stimulation inhibited basal and growth factor-stimulated [(3)H]thymidine incorporation by 74%, and this was mitigated by p38 inhibition. In contrast, alpha(1D)-adrenoceptor stimulation enhanced cellular growth by 136%, and this was blocked by two distinct inhibitors of ERK activation. We conclude that within a given cell type alpha(1)-adrenoceptor subtypes can have opposite effects on cellular growth, although their proximal signal transduction displays only quantitative differences.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Keffel S,Alexandrov A,Goepel M,Michel MC

doi

10.1006/bbrc.2000.2850

subject

Has Abstract

pub_date

2000-06-16 00:00:00

pages

906-11

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)92850-X

journal_volume

272

pub_type

杂志文章

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