RESUMO
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.
Assuntos
Dinoprostona/farmacologia , Agonistas dos Receptores Histamínicos/farmacologia , Histamina/farmacologia , Neurônios Aferentes/efeitos dos fármacos , Animais , Cálcio/metabolismo , Células Cultivadas , Colforsina/farmacologia , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Interações Medicamentosas , Gânglios Espinais/citologia , Inositol 1,4,5-Trifosfato/metabolismo , Isoquinolinas/farmacologia , Modelos Biológicos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Sulfonamidas/farmacologia , Fatores de TempoRESUMO
This paper describes the outcome of user trials of the Nordic Musculoskeletal Questionnaire which encompassed the views of the following groups: data entry clerks, technical staff, administrative clerks and 481 subjects employed in 10 supermarkets. A significant number of improvements was identified, especially concerning its wording, layout and administration. This has led to a standardized version being produced for use in studying the prevalence of reported symptoms in many types of occupational groups.
