The spleen is a multifunction organ that sits at a unique intersection between the circulatory, immune, and neurologic systems. The work in this dissertation endeavored to shed light on the interaction of the sympathetic nervous system in the spleen with these other vital biologic systems. In addition, the role of signaling by the cannabinoid receptors 1 and 2 was explored as it relates the function of splenic sympathetic innervation. Specifically, it was found that splenic noradrenergic neurons do not play a role in T cell independent humoral immunity, and that both norepinephrine and adenosine mediate spleen contraction. It was discovered that splenic sympathetic noradrenergic neurons are likely not regulated by CB1 and that cannabinoid-mediated immunosuppression of humoral immunity is likely due solely to CB2 on immune cells. It was also found that CB1/CB2 play a permissive role in maintaining the relationship between NE release from splenic sympathetic neurons and spleen contraction. These findings add to the knowledge base regarding both the spleen and extra-CNS cannabinoid effects and can be built upon for a more complete understanding of these systems.
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