Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atopic dermatitis is a pruritic, inflammatory cutaneous disorder found most frequently among patients with a personal or family history of atopic disease. A primary defect is found in bone marrow cells. The most consistent abnormality relates to the overproduction of IgE. Pharmacophysiologic abnormalities include abnormal vascular responses, abnormal sweating responses, and a reduced threshold for itch. In addition, seven of 12 patients with pure atopic dermatitis with no respiratory disease have an abnormal methacholine inhalation test. There is an abnormal response of leukocyte cyclic AMP to a variety of adenylate cyclase stimulants. Characteristic histological findings are interepidermal edema, called spongiosis, which is consistent with a composite of late-phase and delayed hypersensitivity. The brittle stratum corneum can be treated with hydration, a commonly neglected aspect of management. An overlooked complication is herpes simplex infection of the eye. Overall management includes stress control, treating allergenic trigger factors, topical steroids, systemic antibiotics, antihistamines, ultraviolet light, and hospitalization in severe cases.
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PMID:Recognizing and managing clinical problems in atopic dermatitis. 248 93

Histamine is present in the epidermis in intracellular and extracellular area and is released from mast cells and keratinocytes in the early stage of inflammation of the skin. Such release may contribute to common itching or intensify the inflammatory responses. Histamine binds to its receptors and participate in regulation of the inflammatory responses by acting on endothelial cells, nerve endings, lymphocytes, monocytes, and leukocytes. Histamine has direct effects on keratinocytes as well. Histamine modulates the proliferation of keratinocytes. The binding of histamine to the receptor on keratinocyte membrane induces activation of adenylate cyclase and phospholipase C through GTP binding protein. We previously reported that histamine induces transient increase in intracellular Ca2+ in cultured normal human epidermal keratinocytes (NHEK) and normal epidermis. H1 and H2 histamine receptors are widely distributed in many tissues and cells. In this study, we investigated which types of histamine receptors are related to the increase in intracellular Ca2+ by histamine stimulation in cultured human epidermal keratinocytes. NHEK were cultured in serum-free KGM medium. With H1 antihistamines, mepyramine and diphenhydramine, histamine responses were moderately but not statistically significantly inhibited. With H2 antihistamine, cimetidine, histamine response was significantly inhibited. Epinephrine response was not affected by these antihistamines. Thus, it is considered that H2 antihistamines specifically block histamine-mediated increase in intracellular Ca2+ of cultured normal human keratinocytes.
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PMID:H2 histamine receptor-mediated increase in intracellular Ca2+ in cultured human keratinocytes. 1051 81

The therapeutic use of cannabinoids, the components of cannabis sativa L., was investigated in numerous researches in detail. Animal studies revealed that cannabinoid receptor agonists alter pain-associated behaviour, have immune-suppressive properties, suppress tumor growth, modulate sensitisation processes and influence memory and learning. Those effects are mediated by two membrane-bound cannabinoid receptors and as mechanisms of signal transduction blockade of ion channels, inhibition of adenylate cyclase and retrograde inhibition of neurotransmitter release are currently being discussed. In clinical studies oral administration of cannabinoids indicated beneficial results during the therapy of multiple sclerosis, weight loss, nausea and vomiting due to chemotherapy, and intractable pruritus. However, therapy of chronic pain conditions revealed conflicting results and unequivocal success could not have been delivered due to unwanted side effects. Further multicentre studies are required to estimate cannabinoids as novel therapeutic tools for the treatment of chronic pain.
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PMID:[Cannabinoids--signal transduction and mode of action]. 1554 20

Primary biliary cirrhosis (PBC) is a chronic liver disease characterized by severe intraepatic cholestasis. Pruritus often occurs during the course of the illness. We designed a study aimed at assessing whether pruritus is associated with dysfunction of signal transduction. Seventeen female patients affected by PBC were enrolled into the study and divided in two groups according to severity of liver disease. Leukocytes were isolated from peripheral blood and Gi, Go and Gs protein expressions were evaluated by western blotting, while G protein function was assessed by measuring cyclic adenosine phosphate formation. The expression of all types of G proteins was increased in leukocytes of PBC patients. The basal adenylate activity was significally higher than control in patients with less severe liver disease, while it was lower than normal in those with severe liver disease. Incubation of patient leukocytes with guanosine triphosphate-gamma-S and Gs protein activators failed to enhance cAMP production, while N-formyl-met-leu-phe was more effective in reducing cAMP production. The expression of all G proteins was non-selectively increased in PBC leukocytes, while adenylate cyclase activity was significantly modified. However, the observed changes in G proteins expression and in adenylate cyclase activity are not related to the presence of pruritus.
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PMID:G protein-mediated signal transduction is affected in primary biliary cirrhosis. 1656 23

Primary sensory neurons in the dorsal root ganglia and trigeminal ganglia are responsible for sensing mechanical and thermal stimuli, as well as detecting tissue damage. These neurons express ion channels that respond to thermal, mechanical, or chemical cues, conduct action potentials, and mediate transmitter release. These neurons also express a large number of G-protein coupled receptors, which are major transducers for extracellular signaling molecules, and their activation usually modulates the primary transduction pathways. Receptors that couple to phospholipase C via heterotrimeric Gq/11 proteins and those that activate adenylate cyclase via Gs are considered excitatory; they positively regulate somatosensory transduction and they play roles in inflammatory sensitization and pain, and in some cases also in inducing itch. On the other hand, receptors that couple to Gi/o proteins, such as opioid or GABAB receptors, are generally inhibitory. Their activation counteracts the effect of Gs-stimulation by inhibiting adenylate cyclase, as well as exerts effects on ion channels, usually resulting in decreased excitability. This review will summarize knowledge on Gi-coupled receptors in sensory neurons, focusing on their roles in ion channel regulation and discuss their potential as targets for analgesic and antipruritic medications.
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PMID:Inhibitory Gi/O-coupled receptors in somatosensory neurons: Potential therapeutic targets for novel analgesics. 2958 Jan 54