DISTRIBUTION AND LOCALISATION OF G alpha PROTEINS IN THE ROSTRAL VENTROLATERAL MEDULLA OF NORMOTENSIVE AND HYPERTENSIVE RATS: FOCUS ON CATECHOLAMINERGIC NEURONS

作者：Parker L M; Tallapragada V J; Kumar N N; Goodchild A K^*

来源：Neuroscience, 2012, 218: 20-34.

DOI：10.1016/j.neuroscience.2012.05.037

• rostral ventrolateral medulla
• rostral C1
• A1
• A5
• G-proteins
• spontaneously hypertensive rat

About 860 G-protein-coupled receptors (GPCRs) mediate their actions via heterotrimeric G-proteins. Their activation releases G alpha from G beta lambda subunits. The type of G alpha subunit dictates the major signalling proteins involved: adenylyl cyclase, PLC and rhoGEF. The rostral ventrolateral medulla (RVLM), containing the rostral C1 (rC1) cell group, sets and maintains the tonic and reflex control of blood pressure and a plethora of inputs converge onto these neurons. We determined the relative abundance of 10 G alpha subunit mRNAs, representing the four major families, within the RVLM, using quantitative RT-PCR. In situ hybridisation (ISH) combined with immunohistochemistry (IHC) was used to quantify and compare this expression in rC1 with that in the A1 and A5 cell groups. The relative abundance of G alpha subunit mRNAs and a comparison of gene expression levels were quantitatively determined in normotensive and hypertensive rat strains. All 10 G alpha mRNAs were detected in the RVLM of Sprague-Dawley (SD) rats with relative abundance such that G alpha s %26gt; G alpha i2 %26gt; G alpha o %26gt; G alpha q %26gt; G alpha L %26gt; G alpha 11 %26gt; G alpha i3 %26gt; G alpha i1 %26gt; G alpha 12 %26gt; G alpha 13. The high abundance of G alpha mRNAs signalling via adenylyl cyclase indicates the importance of associated GPCRs. Within the rC1 and A1 groups similar differential G alpha mRNA expression profiles were seen with G alpha s being found in all rC1 cells, G alpha 11 absent and G alpha i3 rarely expressed. Thus functionally distinct subgroups exist within the rC1 and A1 cell groups as differing distributions of G alpha subunits must reflect the array of GPCRs that influence their activity. In contrast, all A5 cells expressed all G alpha mRNAs suggesting a functionally homogeneous group. When the 10 G alpha mRNAs of the RVLM in spontaneously hypertensive rats (SHR) were compared quantitatively to Wistar-Kyoto (WKY), only G alpha s and G alpha 12 were significantly elevated. However when the expression in normotensive SD and WKY was compared with SHR no significant differences were evident. These findings demonstrate a range of GPCR signalling capabilities in brainstem neurons important for homeostasis and suggest a prominent role for signalling via adenylyl cyclase.

• 出版日期2012-8-30