histamine H4 receptor; HH4R; G-protein coupled receptor 105; GPRv53; SP9144; AXOR35; Pfi-013 (HRH4, GPCR105)
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Function
- the H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues
- displays a significant level of constitutive activity (spontaneous activity in the absence of agonist)
Structure
belongs to the G-protein coupled receptor 1 family
Compartment
Expression
- expressed primarily in the bone marrow & eosinophils
- preferential expression in cells of immunological relevance such as T-cells, dendritic cells, monocytes, mast cells, neutrophils
- also expressed in a wide variety of peripheral tissues, including the heart, kidney, liver, lung, pancreas, skeletal muscle, prostate, small intestine, spleen, testis, colon, fetal liver & lymph node
- expression is either up-regulated or down-regulated upon activation of the lymphoid tissues
Pharmacology
- does not bind diphenhydramine, loratadine, ranitidine, cimetidine or chlorpheniramine
- shows shows modest affinity for dimaprit, impromidine, clobenpropit, thioperamide, burimamide clozapine, immepip & imetit
- the order of inhibitory activity is imetit > clobenpropit > burimamide > thioperamide
- clobenpropit behaves as a partial agonist
- dimaprit & impromidine show some agonist activity
- clozapine behaves as a full agonist
- thioperamide shows inverse agonism (enhances cAMP activity)
- the order of inhibitory activity of histamine derivatives was histamine > N-alpha-methylhistamine > R(-)-alpha- methylhistamine > S(+)-alpha-methylhistamine
- both N-alpha-methylhistamine > R(-)-alpha-methylhistamine behave as full agonists