Reduced Noradrenergic Signaling in the Spleen Capsule in the Absence of CB1and CB2Cannabinoid 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 CB1and CB2cannabinoid 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 CB1receptor signaling. Thus, these studies demonstrate a role for CB1and/or CB2in noradrenergic splenic contraction.
Neuroscience Program, Michigan State University, East Lansing, MI, USA.|Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
Tyrell J
TJ
Simkins
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
David
D
Fried
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Kevin
K
Parikh
Neuroscience Program, Michigan State University, East Lansing, MI, USA.|Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
James J
JJ
Galligan
Neuroscience Program, Michigan State University, East Lansing, MI, USA.|Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.|Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
John L
JL
Goudreau
Neuroscience Program, Michigan State University, East Lansing, MI, USA.|Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.|Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
Keith J
KJ
Lookingland
Neuroscience Program, Michigan State University, East Lansing, MI, USA. bkaplan@cvm.msstate.edu.|Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA. bkaplan@cvm.msstate.edu.|Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. bkaplan@cvm.msstate.edu.|Department of Basic Sciences, Mississippi State University, PO Box 6100, Mississippi State, MS, 39762, USA. bkaplan@cvm.msstate.edu.
Barbara L F
BL
Kaplan
D059331:Adrenergic Neurons / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D005260:Female; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D043884:Receptor, Cannabinoid, CB1 / Q000172:deficiency*; D043885:Receptor, Cannabinoid, CB2 / Q000172:deficiency*; D013154:Spleen / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*
D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D009638:Norepinephrine
Cannabinoids; Contraction; Noradrenergic; Spleen