The inflammatory mediators serotonin, prostaglandin E2 and bradykinin evoke calcium influx in rat sensory neurons.
The inflammatory mediators bradykinin, prostaglandin E(2) and serotonin interact to excite and sensitize nociceptive neurons. All three mediators are coupled to signaling pathways that potentially induce rises in intracellular calcium concentration in other models. The aim of this study was therefore to investigate if the three mediators cause calcium rises in isolated rat sensory neurons that may explain their sensitizing action. Neurons exposed to serotonin, bradykinin, and prostaglandin E(2) exhibited reversible increases in intracellular calcium concentration, which were absent in calcium-free solution. The calcium increase induced by serotonin was preserved in the presence of extracellular cadmium suggesting calcium influx potentially through the serotonin receptor ion channel 5-HT(3). The bradykinin-induced calcium response was slower, showed pronounced tachyphylaxis and was absent in the presence of extracellular cadmium ions. Similar results were obtained for prostaglandin E(2) although the calcium rises were fast and not prone to tachyphylaxis. This suggests that prostaglandin E(2) as well as bradykinin via activation of G protein-coupled receptors seem to couple to calcium-permeant ion channels possibly the heat-transducing vanilloid receptor type 1 or related ion channels. The three mediators, however, did not cooperate to induce supra-additive calcium responses when applied simultaneously. In summary, our results suggest that the inflammatory mediators serotonin, prostaglandin E(2) and bradykinin induce calcium influx in sensory neurons. However, they do not utilize a calcium-dependent cooperative mechanism to facilitate proton-induced currents.
Linhart
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O
Institut fur Physiologie und Experimentelle Pathophysiologie, Universitaetsstrasse 17, D-91054, Erlangen, Germany.
Obreja
O
O
Kress
M
M
D000818:Animals; D001920:Bradykinin / Q000378:metabolism* / Q000494:pharmacology; D002104:Cadmium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism* / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology
D018836:Inflammation Mediators; D007473:Ion Channels; D011955:Receptors, Drug; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D002104:Cadmium; D012701:Serotonin; D015232:Dinoprostone; D001920:Bradykinin; D002118:Calcium