Angiotensin At₁Receptor Signalling Pathways In Neurons

Abstract

1. The aim of the present article is to review the intracellular signal transduction pathways that are influenced by the peptide angiotensin (Ang) II, acting via its type 1 (AT1) receptor, in neurons. 2. The AT1 receptors couple to a wide variety of signalling pathways in peripheral tissues, such as kidney, heart and vascular smooth muscle. A similar diversity of signalling mechanisms exists for AT1 receptors in neurons. 3. We outline the known neuronal AT1 receptor signalling pathways as they relate to function. Pathways that couple activation of AT1 receptors to short-term changes in neuronal membrane ionic currents and firing rate will be reviewed. These are different from the pathways that elicit longer-term changes in enzyme activity and gene expression and, ultimately, increases in noradrenaline synthesis. 4. Novel AT1 receptor signalling pathways discovered through gene expression profiling and their potential functional significance have been discussed.

Lack of Macrophage Migration Inhibitory Factor Regulation Is Linked to the Increased Chronotropic Action of Angiotensin II in SHR Neurons

“…Ang IIinduced increases in MIF involve activation of a calciumdependent PKC but not calcium-calmodulin-dependent kinase II. 9 Because the MIF gene promoter contains several sites (eg, activation protein-1 and cyclic AMP response element) that may be indirectly influenced by PKC, 24 it is possible that PKC directly or indirectly modulates MIF gene expression. More recently, we have determined that ROS (specifically H 2 O 2 ) can induce MIF expression in normotensive rat cultured neurons.…”

“…AT1R-specific binding was assessed in WKY rat and SHR neuronal cultures, treated as above with viral vectors or PBS using 125 I-(Sar 1 -Ile 8 )-Ang II, as described previously. 9 …”

“…7,21 These data are supported by our in vitro studies indicating that AT1R expression and the chronotropic action of Ang II are enhanced in neurons cultured from the SHR hypothalamus and brain stem. 9,22 There are various possible explanations for the hyperactivity of AT1R-mediated actions of Ang II in SHR neurons, including the following: (1) amplification of the neuronal intracellular signaling pathways that underlie Ang II actions; (2) specific intracellular mechanisms that do not exist in normotensive rat neurons are activated in SHR neurons; and (3) regulatory mechanisms that are present in normotensive rat neurons are lacking in SHR neurons. Considering our findings that MIF can serve as a negative regulator of Ang II actions in normotensive rat neurons, we examined whether this mechanism is present in SHR neurons.…”

NADPH Oxidase Contributes to Angiotensin II Signaling in the Nucleus Tractus Solitarius

“…In neurons, one of the better characterized pathways involves activation of phospholipase C through AT 1 receptors, followed by hydrolysis of phosphoinositide and increased Ca 2ϩ release from intracellular stores (Sumners et al, 2002). The increase in Ca 2ϩ then leads to activation of a wide variety of pathways that mediate the short-and long-term effects of AngII (Berry et al, 2001).…”

Role of Angiotensin II in Nucleus Tractus Solitarius

“…In muscle cells, Ang stimulates phospholipase C (PLC), the production of inositol 1,4,5 trisphosphate (IP3) and diacylglycerol (DAG), and the mobilization of [Ca 2+ ]i 65) . In neurons, one of the better characterized pathways involves activation of phosphoinositide and increased Ca 2+ release from intracellular stores 66) .…”