Temperature dependency of basal and evoked release of amino acids and calcitonin gene-related peptide from rat dorsal spinal cord.
Moderate hypothermia significantly diminishes consequences of spinal and cerebral anoxia. One component of this neuroprotection has been hypothesized to be suppression of excitotoxic transmitter release. Whether this suppression is attributable to reduced hypoxic injury that induces release or an alteration of the release process itself is unclear. We sought to characterize the temperature sensitivity (Q10) of basal and evoked calcitonin gene-related peptide (CGRP) and amino acid release from dorsal horn slices of rat spinal cord over a range of temperatures from 40 to 8 degrees C. At 40 degrees C, potassium (60 mM) and capsaicin (10 microM) evoked a 21- and 32-fold increase in basal CGRP concentrations, respectively. Capsaicin had no effect on glutamate release, but potassium evoked a 2.7-fold increase. Release evoked by either potassium or capsaicin was reduced in a biphasic fashion with declining temperature. Over the range of 40 to 34 degrees C, the Q10 values for evoked release for CGRP were 11.3 (potassium) and 39.7 (capsaicin) and for glutamate, 5. 5 (potassium). Over the range of 34 to 8 degrees C, Q10 values were near unity for all evoked release (0.8 and 1.3 for CGRP and 1.2 for glutamate). Although serine, glycine, glutamine, taurine, and citrulline showed no evoked release, basal levels were reduced at temperatures below 34 degrees C. The pronounced temperature dependency of evoked transmitter release between 40 and 34 degrees C is consistent with the profound cerebral protection observed with mild hypothermia in which metabolic activity is only slightly depressed.
Dirig
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DM
Department of Pharmacology, University of California, San Diego, La Jolla, California 92093-0818, USA.
Hua
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XY
Yaksh
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D000818:Animals; D001224:Aspartic Acid / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D001831:Body Temperature; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003429:Cross Reactions; D005334:Fever / Q000378:metabolism / Q000503:physiopathology*; D018698:Glutamic Acid / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D005998:Glycine / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D007035:Hypothermia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009924:Organ Culture Techniques; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D001224:Aspartic Acid; D018698:Glutamic Acid; D012694:Serine; D015740:Calcitonin Gene-Related Peptide; D011188:Potassium; D002211:Capsaicin; D002118:Calcium; D005998:Glycine