Modulation of angiotensin II type 2 receptor mRNA in rat hypothalamus and brainstem neuronal cultures by growth factors.
This study investigates the regulatory effects of growth factors upon angiotensin II type 2 (AT2) mRNA levels in neurons co-cultured from newborn rat hypothalamus and brainstem. Incubation of cultured neurons with nerve growth factor (NGF; 5-50 ng/ml) caused time-dependent changes in the steady-state levels of AT2 receptor mRNA. Short-term (0.5-1.0 h) incubations with NGF resulted in significant increases in AT2 receptor mRNA, whereas longer-term incubations (4-24 h) caused significant decreases. Activation of NGF receptors is known to stimulate phospholipase C-gamma and subsequently activate protein kinase C (PKC). Incubation of cultures with the PKC activator, phorbol-12-myristate-13-acetate (PMA; 100 nM), caused temporal changes in AT2 receptor mRNA levels similar to those observed with NGF. By contrast, insulin (0.1-10 microg/ml) elicited only significant decreases in AT2 receptor mRNA levels. The observed abilities of NGF and insulin to regulate the expression of AT2 receptor mRNA are consistent with the fact that the AT2 receptor gene promoter region contains several cis DNA regulatory elements that respond to growth factor-stimulated transcription factors. These novel observations which show that NGF and insulin can regulate AT2 receptor mRNA in neurons derived from neonatal rat CNS lend support to the idea that AT2 receptors have a role in development and differentiation.
Huang
X C
XC
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.
Shenoy
U V
UV
Richards
E M
EM
Sumners
C
C
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000187:drug effects*
D007328:Insulin; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011945:Receptors, Angiotensin