Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB sub(1) and CB sub(2) 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 alpha 2-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 sub(1) and CB sub(2) cannabinoid receptors (Cnr1 super( -/- ) /Cnr2 super( -/- ) 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 super( -/- ) /Cnr2 super( -/- ) mouse spleens, likely due to decreased expression of capsular alpha 1AR. The majority of splenic Cnr1 mRNA expression is by cells of the spleen capsule, suggestive of post-synaptic CB sub(1) receptor signaling. Thus, these studies demonstrate a role for CB sub(1) and/or CB sub(2) in noradrenergic splenic contraction.