Ch. Gelband et al., ANGIOTENSIN RECEPTORS AND NOREPINEPHRINE NEUROMODULATION - IMPLICATIONS OF FUNCTIONAL COUPLING, Regulatory peptides, 72(2-3), 1997, pp. 139-145
The objective of this review is to examine the role of neuronal angiot
ensin II (Ang II) receptors in vitro. Two types of G protein-coupled A
ng II receptors have been identified in cardiovascularly relevant area
s of the brain: the AT(1) and the AT(2). We have utilized neurons in c
ulture to study the signaling mechanisms of AT(1) and AT(2) receptors.
Neuronal AT(1) receptors are involved in norepinephrine (NE) neuromod
ulation. NE neuromodulation can be either evoked or enhanced. Evoked N
E neuromodulation involves AT(1) receptor-mediated, losartan-dependent
, rapid NE release, inhibition of K+ channels and stimulation of Ca2channels. AT(1) receptor mediated enhanced NE neuromodulation involves
the Ras-Raf-MAP kinase cascade and ultimately leads to an increase in
NE transporter, tyrosine hydroxylase and dopamine beta-hydroxylase mR
NA transcription. Neuronal AT(2) receptors signal via a G(i) protein a
nd are coupled to activation of PP2A and PLA(2) and stimulation of Kchannels. Finally, putative cross-talk pathways between AT(1) and AT(2
) receptors will be discussed. (C) 1997 Elsevier Science B.V.