THE ANGIOTENSIN AT(2) RECEPTOR DOWN-REGULATES NEUROFILAMENT-M IN PC12W CELLS

The angiotensin (ANG II) AT(2) receptor mediates antiproliferative eff ects and induces neurite outgrowth in PC12W cells. To further investig ate the molecular events following AT(2) receptor stimulation in these cells, we determined the expression pattern of the middle-sized neuro filament subunit (NF-M) using Western and Northern blot analysis and r everse-transcription polymerase chain reaction. On both, the protein a nd the mRNA level, ANG TI via AT(2) receptors not only counteracted ne rve growth factor (NGF)-mediated NF-M up-regulation but also reduced N F-M levels in the absence of NGF by maximally 72%. The ANG II-induced effects were completely abolished by pretreatment with the AT(2) recep tor antagonist, PD123177. In view of previous findings of decreased NF levels in regenerating neurons and in neuronal cultures undergoing ap optosis, our observation suggests a new role of AT(2) receptors in eit her of these processes. (C) 1997 Elsevier Science Ireland Ltd.