ERK activation by G-protein-coupled receptors in mouse brain is receptor identity-specific.
In transfected cells and non-neuronal tissues many G-protein-coupled receptors activate p44/42 MAP kinase (ERK), a kinase involved in both hippocampal synaptic plasticity and learning and memory. However, it is not clear to what degree these receptors couple to ERK in brain. G(s)-coupled beta-adrenergic receptor activation of ERK in neurons is critical in the regulation of synaptic plasticity in area CA1 of the hippocampus. In addition, alpha(1)- and alpha(2)-adrenergic receptors, present in CA1, could potentially activate ERK. We find that, like the beta-adrenergic receptor, the G(q)-coupled alpha(1)AR activates ERK in adult mouse CA1. However, activation of the G(i/o)-coupled alpha(2)AR does not activate ERK, nor does activation of a homologous G(i/o)-coupled receptor enriched in adult mouse CA1, the 5HT(1A) receptor. In contrast, the nonhomologous G(i/o)-coupled gamma-aminobutyric acid type B receptor does activate ERK in adult mouse CA1. Surprisingly, activation of alpha(2)ARs in CA1 from immature animals where basal phospho-ERK is low induces ERK phosphorylation. These data suggest that although most G-protein-coupled receptor subtypes activate ERK in non-neuronal cells, the coupling of G(i/o) to ERK is tightly regulated in brain.
Vanhoose
Amanda M
AM
Department of Molecular Physiology and Biophysics, and the Center for Molecular Neuroscience, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Emery
Megan
M
Jimenez
Lismary
L
Winder
Danny G
DG
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology
D018341:Receptors, Adrenergic, alpha-2; D018342:Receptors, Adrenergic, beta-1; D011956:Receptors, Cell Surface; D018080:Receptors, GABA-B; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins