TY - JOUR
T1 - Morphine and norepinephrine but not 5-hydroxytryptamine and γ-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices
AU - Pang, Iok-Hou
AU - Vasko, Michael R.
PY - 1986/6/25
Y1 - 1986/6/25
N2 - We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 × 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37°C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10-4 and 10-5 M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10-5M) and phentolamine (10-5M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10-4 M and 10-4 M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord.
AB - We studied whether morphine, norepinephrine (NE), 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) inhibit the potassium-stimulated release of substance P (SP) from rat spinal cord slices. Male Sprague-Dawley rats were decapitated and a 2-cm segment of lumbosacral spinal cord was removed, chopped into 0.5 × 0.5 mm pieces, weighed, placed in a perfusion chamber and perfused at 37°C with a modified Krebs bicarbonate buffer. Perfusate was collected, lyophilized, then assayed for SP using radioimmunoassay. Exposure of spinal cord tissue to 50 mM KCl for 8 min produced a calcium-dependent increase in the release of SP from a basal level of approximately 0.1 pg/mg tissue/min to 0.3 pg/mg tissue/min. Morphine and NE at concentrations of 10-4 and 10-5 M did not alter basal release but caused a significant reduction in the potassium-stimulated release of SP. Naloxone (10-5M) and phentolamine (10-5M) did not affect SP release but attenuated the effects of morphine and NE, respectively. Naloxone did not antagonize the inhibition of release produced by NE nor did phentolamine block the effect of morphine, suggesting that the actions of the agonists are independent. In contrast, 5-HT and GABA at concentrations of 10-4 M and 10-4 M did not significantly alter the basal or potassium-stimulated release of SP. These results demonstrate a differential regulation of SP release in the spinal cord and support the hypothesis that morphine and NE may modify nociception, in part, by inhibiting the release of SP in the spinal cord.
KW - morphine
KW - norepinephrine
KW - potassium-stimulated release
KW - serotonin
KW - substance P
KW - γ-aminobutyric acid
UR - http://www.scopus.com/inward/record.url?scp=0022468074&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(86)90189-7
DO - 10.1016/0006-8993(86)90189-7
M3 - Article
C2 - 2425894
AN - SCOPUS:0022468074
VL - 376
SP - 268
EP - 279
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 2
ER -