Regulation of cAMP levels in area CA1 of hippocampus by Gi/o-coupled receptors is stimulus dependent in mice.

Vanhoose AM, Ritchie MD, Winder DG
Neurosci Lett. 2004 370 (1): 80-3

PMID: 15489022 · DOI:10.1016/j.neulet.2004.07.093

The cAMP signaling cascade plays a critical role in regulating synaptic efficacy and cellular excitability in hippocampus. Adenylyl cyclase (AC) activation and subsequent generation of cAMP occurs through a number of mechanisms in area CA1 of hippocampus, including Galpha(s)-mediated stimulation upon G-protein coupled receptor (GPCR) activation and Ca2+ -mediated stimulation upon NMDA receptor activation. In addition, activation of Gi/o-coupled receptor subtypes can regulate cAMP levels through modulation of AC activity. Multiple Gi/o-coupled receptor subtypes are expressed in area CA1, where they are commonly thought to dampen synaptic transmission and excitability, in part through inhibition of AC activity and cAMP generation. However, a large family of ACs exists, and in recombinant systems, the cAMP signals generated by these AC isoforms are both inhibited and enhanced by Gi/o-coupled receptors in a manner dependent on the AC isoform and stimulus. Thus, we have assessed the effects of activating several different Gi/o-coupled receptors on the generation of cAMP induced either by NMDA receptor activation or by beta-adrenergic receptor activation within area CA1 of mouse hippocampus. We find that in situ the effect of Gi/o-coupled receptor activation does indeed depend upon the means by which ACs are activated. In addition, the effects are also Gi/o-coupled receptor-specific, suggesting additional complexity. These data indicate that Gi/o-coupled receptors may play roles in "routing" second messenger signaling in area CA1.

MeSH Terms (27)

8-Hydroxy-2-(di-n-propylamino)tetralin Adrenergic alpha-Agonists Adrenergic beta-Agonists Analysis of Variance Animals Baclofen Brimonidine Tartrate Calcium Cyclic AMP Dopamine Agonists Drug Interactions Excitatory Amino Acid Agonists GABA Agonists GTP-Binding Protein alpha Subunits, Gi-Go Hippocampus In Vitro Techniques Isoproterenol Male Mice Mice, Inbred C57BL N-Methylaspartate Quinoxalines Quinpirole Radioimmunoassay Receptors, G-Protein-Coupled Receptors, N-Methyl-D-Aspartate Serotonin Receptor Agonists

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