α1-Adrenoceptor subtypes differentially couple to growth promotion and inhibition in Chinese hamster ovary cells

We have compared the coupling of human alpha(1A)-, alpha(1B)-, and alpha(1D)-adrenoceptors (expressed at approximate to 2000 fmol/mg protein in Chinese hamster ovary cells) to cellular growth promotion (as assessed by [H-3]thymidine incorporation) and related signaling mechanisms. Maximum elevation of intracellular Ca2+ by the three subtypes occurred with the rank order a, (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 [H-3]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. (C) 2000 Academic Press.