Purinergic Receptor P2Y1 Modulates Catecholamine Signaling in Murine Mesenteric Lymph Nodes.

Abstract

Neuroimmune communication is crucial for the body's response to physiological challenges, homeostasis, and immune stress response. Adrenergic and purinergic neurotransmission in the sympathetic nervous system is vital for this communication. This study achieves the first co-detection of adenine-based purines and catecholamines in mesenteric lymph nodes via fast-scan cyclic voltammetry. Additionally, we reveal that manipulating an ATP receptor can impact catecholamine signaling in the lymph node for the first time. The G-protein-coupled receptor P2Y1, which controls intracellular Ca²⁺ levels, was targeted with the antagonist MRS2179. MRS2179 decreased catecholamine concentrations, increased inter-event times, and prolonged event durations. These results suggest that events became smaller, less frequent, and longer-lasting, possibly attributable to decreased intracellular Ca²⁺ levels. These findings indicate that ATP release in the lymph node can partially regulate norepinephrine signaling, providing mechanistic insight into sympathetic neuronal neurotransmitter control. A deeper understanding of more complicated neuroimmune mechanisms could potentially influence the development of therapeutic strategies in immunology and neurobiology.