Prostaglandin E2 sensitizes primary sensory neurons to histamine

• Published in: Neuroscience 2007-11, Vol.150 (1), p.22-30
• Main Authors: Nicolson, T.A, Foster, A.F, Bevan, S, Richards, C.D
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cells, Cultured; Colforsin - pharmacology; Cyclic AMP - metabolism; Dinoprostone - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Histamine - pharmacology; Histamine Agonists - pharmacology; Inositol 1,4,5-Trisphosphate - metabolism; Isoquinolines - pharmacology; Models, Biological; Neurology; Neurons, Afferent - drug effects; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sulfonamides - pharmacology; Time Factors; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.09.003

Abstract 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 μM). 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 μM PGE2. 3. The phospholipase C (PLC) inhibitor 1-[6-[[17-β-3-methoxyestra-1,3,5(10)-trien-17-yl-]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) completely blocked the response to histamine (100 μM) 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.