Regulation of cAMP levels in area CA1 of hippocampus by Gi/o-coupled receptors is stimulus dependent in mice.
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.
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Room 724B, RRB, Nashville, TN 37232-0615, USA.
Amanda M
AM
Vanhoose
Marylyn D
MD
Ritchie
Danny G
DG
Winder
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D000068438:Brimonidine Tartrate; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D011863:Radioimmunoassay / Q000379:methods; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D011810:Quinoxalines; D043562:Receptors, G-Protein-Coupled; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; D019257:Quinpirole; D000068438:Brimonidine Tartrate; D016202:N-Methylaspartate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000242:Cyclic AMP; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D001418:Baclofen; D007545:Isoproterenol; D002118:Calcium