The histamine receptor H3 is a Gi-coupled GPCR expressed in the thalamus, caudate nucleus, putamen, cerebellum, amygdala, substantia nigra, hippocampus, hypothalamus and cerebral cortex. Activation of H3 receptor in human nasal mucosa inhibits sympathetic vasoconstriction. Expression of human H3 receptor splice variants in CHO cells shows that a deletion in the 2nd transmembrane domain alters ligand binding and deletions in the 3rd intracellular loop result in signal transduction being abolished.