Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Histamine is able to elicit a dose-dependent rise in intracellular Ca2+ in a proportion of rat dorsal root ganglion (DRG) neurons. Pre-treatment with prostaglandin (PGE2) prior to a histamine challenge increases the proportion of neurons responding to low concentrations of histamine (10-100 microM). 2. The dose-response curve for histamine is shifted to the left by approximately two orders of magnitude following 45 s pre-treatment with 1 microM PGE2. 3. The phospholipase C (PLC) inhibitor 1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl-]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) completely blocked the response to histamine (100 microM) in non-sensitized cells but, after PGE2 pre-treatment, this inhibitor reduced the proportion of cells responding to histamine by approximately a half. Removal of extracellular Ca2+ blocked the response in the remaining cells so that, in this subgroup of histamine sensitive neurons, the PGE2 sensitization is the result of activation of a Ca influx pathway. 4. The sensitization is dependent on an increase in cAMP as it is mimicked by pre-treatment with 8-bromo cyclic AMP (8-Br-cAMP) and by forskolin stimulation of adenylyl cyclase activity. It is inhibited by THFA (tetrahydrofuryl adenine) an inhibitor of adenylyl cyclase. The sensitization is also blocked by pre-treatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), an inhibitor of protein kinase A. We conclude that the PGE2 sensitization of DRG neurons to histamine is dependent on activation of the cAMP-protein kinase A cascade.
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PMID:Prostaglandin E2 sensitizes primary sensory neurons to histamine. 1794 28