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<p>Spaceflight-induced cardiac atrophy and rhythm disorders are linked to dysregulation of the adrenergic-cAMP-PKA pathway. Gravity-dependent alterations in adrenergic signaling, particularly cAMP dynamics, remain poorly understood. Using fluorescence biosensors, we studied intact cells under simulated microgravity and hypergravity. We observed shifts in the EC50 of cAMP production: leftward under hypergravity and rightward in microgravity, with faster cAMP accumulation kinetics in hypergravity. Cytoskeletal remodeling, hypothesized to be a determinant of such changes, was negligible, suggesting alternative mechanisms. These findings highlight significant gravity-induced offsets in the pharmacology of a prototypical G protein-coupled receptor, with implications not only for adrenergic signaling but also for other pathways of pharmacological interest, potentially informing countermeasures for astronaut health and pharmacology in altered gravity settings.</p>

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Effects of altered gravity on adrenergic-mediated cAMP signalling in intact cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月30日

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  • Marc Bathe-Peters,
  • Iqra Sohail,
  • Alexei Sirbu,
  • Katharina Schneider,
  • Tommaso Patriarchi,
  • Anantha Anilkumar,
  • Yannick Lichterfeld,
  • Christian Liemersdorf,
  • Primal de Lanerolle,
  • Paolo Annibale

摘要

Spaceflight-induced cardiac atrophy and rhythm disorders are linked to dysregulation of the adrenergic-cAMP-PKA pathway. Gravity-dependent alterations in adrenergic signaling, particularly cAMP dynamics, remain poorly understood. Using fluorescence biosensors, we studied intact cells under simulated microgravity and hypergravity. We observed shifts in the EC50 of cAMP production: leftward under hypergravity and rightward in microgravity, with faster cAMP accumulation kinetics in hypergravity. Cytoskeletal remodeling, hypothesized to be a determinant of such changes, was negligible, suggesting alternative mechanisms. These findings highlight significant gravity-induced offsets in the pharmacology of a prototypical G protein-coupled receptor, with implications not only for adrenergic signaling but also for other pathways of pharmacological interest, potentially informing countermeasures for astronaut health and pharmacology in altered gravity settings.