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Crosstalk of noradrenergic Ca2+ and cAMP signaling in astrocytes of the murine olfactory bulb

Sauer, J.; Beiersdorfer, A.; Schmidt, F. L.; Nordbeck, M.; Constantin, O.; Hirnet, D.; Gee, C. E.; Lohr, C.

2025-11-11 neuroscience
10.1101/2025.11.10.687535 bioRxiv
Show abstract

Cyclic adenosine monophosphate (cAMP) and Ca2+ are ubiquitous second messengers that regulate gene expression, metabolism, and synaptic plasticity. Here, we identified a complex interplay between Ca2+ and cAMP signaling pathways in mouse olfactory bulb astrocytes. Norepinephrine (NE) elevated both Ca2+ and cAMP levels via 1 and 2 adrenergic receptors, whereas {beta} receptors triggered only cAMP responses. The 1 receptor agonist phenylephrine increased cAMP, but this effect was suppressed when Ca2+ elevations were blocked by Ca2+ depletion and removal of external Ca2+. We found that 1A and 1D receptors are key targets for phenylephrine, acting through Ca2+/calmodulin-dependent adenylyl cyclases AC1 and AC3 downstream of 1 receptor activation. Moreover, 2 receptor stimulation raised Ca2+ levels, thereby stimulating cAMP production, yet also reduced forskolin-induced cAMP elevations, indicating that 2 receptors can both inhibit adenylyl cyclase via Gi and stimulate AC1/AC3 via Ca2+ signaling. Together, these findings reveal intricate crosstalk between noradrenergic Ca2+ and cAMP signaling in olfactory bulb astrocytes mediated by all three adrenergic receptor subtypes.

Published in Cell Communication and Signaling · training set

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