Histamine H3 receptor (Lovenberg TW et al, 1999) is predominantly expressed in the CNS and is involved in decreasing the release of neurotransmitters such as histamine, acetylcholine, norepinephrine and serotonin. There are currently at least six isoforms of the H3 receptor in humans of which isoforms 1,2 and 4 encode functional proteins (Wellendorph P et al, 2002).
Histamine H4 receptor (Nakamura T et al, 2000) is highly expressed in bone marrow and white blood cells. It is also found in other tissues such as colon, liver, lungs and thymus. The H4 receptor mediates mast cell chemotaxis. Both the H3 and H4 receptors mediate their actions by coupling with the G protein alpha-i subtype, thus decreasing intracellular cAMP.