Increased spinal release of excitatory amino acids following intradermal injection of capsaicin is reduced by a protein kinase G inhibitor.
Second messengers have been shown to play a role in the release of neurotransmitters presynaptically in several brain regions and cell types. This study was designed to test the hypothesis that the increased release of aspartate and glutamate that occurs after injection of capsaicin is dependent on activation of the cAMP and the cGMP transduction cascades. A microdialysis fiber was implanted into the dorsal horn of the spinal cord for collection of extracellular fluid and for administration of drugs to the spinal cord. Dialysate samples were collected before and after injection of capsaicin and after infusion of inhibitors of protein kinase G (PKG; KT5823) or protein kinase A (PKA; H89). KT5823, H89, or artificial cerebrospinal fluid (ACSF; control) were administered after injection of capsaicin to reduce the increased release of aspartate and glutamate. At the time of injection of capsaicin, there is an increase in release of aspartate (191+/-21%) and glutamate (194+/-14%). This increased release is maintained through 2.5 h for both glutamate and aspartate at approximately 125% to 150%. The increase in aspartate and glutamate concentrations that occurs after capsaicin injection was reduced back to baseline after spinal infusion of the PKG inhibitor, KT5823. Blockade of PKA had no effect on the increased release of aspartate and glutamate. Thus, the current data support a role for the cGMP-PKG pathway in the control of neurotransmitter release in vivo.
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Physical Therapy Graduate Program, 2600 Steindler Bldg., The University of Iowa, Iowa City, IA 52242-1008, USA.
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D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002211:Capsaicin / Q000008:administration & dosage* / Q000494:pharmacology; D002227:Carbazoles; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D007211:Indoles; D007271:Injections, Intradermal; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*; D013449:Sulfonamides
D000470:Alkaloids; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D007546:Isoquinolines; D013449:Sulfonamides; C073601:KT 5823; D001224:Aspartic Acid; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002211:Capsaicin