ANGIOTENSIN RECEPTORS AND NOREPINEPHRINE NEUROMODULATION - IMPLICATIONS OF FUNCTIONAL COUPLING

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) 1998 Elsevier Science B.V.