Angiotensin receptors and norepinephrine neuromodulation: implications of functional coupling

The objective of this review is to examine the role of neuronal angiotensin II (Ang II) receptors in vitro. Two types of G protein-coupled Ang II receptors have been identified in cardiovascularly relevant areas of the brain: the AT(1) and the AT(2). We have utilized neurons in culture to study the signaling mechanisms of AT(1) and AT(2) receptors. Neuronal AT(1) receptors are involved in norepinephrine (NE) neuromodulation. NE neuromodulation can be either evoked or enhanced. Evoked NE neuromodulation involves AT(1) receptor-mediated, losartan-dependent, rapid NE release, inhibition of K+ channels and stimulation of Ca2+ channels. 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 mRNA transcription. Neuronal AT(2) receptors signal via a G(i) protein and are coupled to activation of PP2A and PLA(2) and stimulation of K+ channels. Finally, putative cross-talk pathways between AT(1) and AT(2) receptors will be discussed. (C) 1998 Elsevier Science B.V.