Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB and CB Cannabinoid Receptors.

The spleen is a visceral organ that contracts during hypoxia to expel erythrocytes and immune cells into the circulation. Spleen contraction is under the control of noradrenergic sympathetic innervation. The activity of noradrenergic neurons terminating in the spleen capsule is regulated by α2-adrenergic receptors (AR). Interactions between endogenous cannabinoid signaling and noradrenergic signaling in other organ systems suggest endocannabinoids might also regulate spleen contraction. Spleens from mice congenitally lacking both CB and CB cannabinoid receptors (Cnr1 /Cnr2 mice) were used to explore the role of endocannabinoids in spleen contraction. Spleen contraction in response to exogenous norepinephrine (NE) was found to be significantly lower in Cnr1 /Cnr2 mouse spleens, likely due to decreased expression of capsular α1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB receptor signaling. Thus, these studies demonstrate a role for CB and/or CB in noradrenergic splenic contraction.