Summary
Regulation of the release of substance P (SP) by the coexisting neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in the ventral spinal cord and the effects of chronic antidepressant treatment mediated changes in serotonin metabolism on the regulation, were examined.
The K+ (40 mmol/l) evoked release of (SP) from slices of the ventral spinal cord of the rat was potentiated by (5-HT) applied to 100 μmol/l concentration. This effect was blocked by the serotoninergic antagonists methysergide (10 μmol/l), methiotepin (10 μmol/l) and fully blocked by ketanserin (10 μmol/l). Thus the 5-HT receptor which regulates the release of SP appears to belong to the type-2 5-HT receptors. Chronic treatment with the selective serotonin uptake inhibitor zimelidine (14 days, 2×10 μmol/kg/day, p.o.) lowered the tissue levels of the 5-HT metabolite: 5-hydroxyindol acetic acid (5-HIAA) and elevated the tissue levels of SP in both the ventral and dorsal spinal cord as compared to that in the vehicle treated group (14 days, 2×5 ml saline/kg/day, p.o.). The decrease in the 5-HIAA levels after chronic zimelidine treatment was quantitatively similar in the dorsal (33%,p<0.01) and ventral (31%,p<0.05) spinal cord. The increase in SP levels after chronic zimelidine treatment was more pronounced in the ventral cord (80%,p<0.01) where the majority of the SP containing nerve endings also contain 5-HT, than in the dorsal spinal cord (22% increase in SP,p<0.05), where only a minor fraction of the SP-containing nerve endings shows a 5-HT/SP coexistence. Chronic treatment with imipramine (14 days, 2×10 μmol/kg/day, p.o.) gave qualitatively similar results to those obtained by zimelidine treatment, but increases in SP levels, and decreases in 5-HT and 5-HIAA levels in ventral and dorsal spinal cord, were less pronounced. The K+ (40 mmol/l) evoked release of SP was studied in a slice preparation of the ventral spinal cord, from rats chronically treated with imipramine, zimelidine and saline. In the zimelidine treated group the amount of SP released (pmol/g tissue) and the fractional SP release upon K+ (40 mmol/l) stimulation was increased by 53% (p<0.01) and 42% (p<0.01) respectively, when compared to the control group. No significant changes in the amount of SP released or fractional SP release were observed when tissue preparations from rats treated with imipramine were used. Thus, it seems that treatment with specific serotoninergic or monoaminergic antidepressant drugs does not only change the tissue levels of the monoamine and its metabolite but also affects the coexisting peptidergic transmitter; SP in the ventral spinal cord. This change is also reflected in the size of the releaseable pool of SP.
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Iverfeldt, K., Peterson, LL., Brodin, E. et al. Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment. Naunyn-Schmiedeberg's Arch. Pharmacol. 333, 1–6 (1986). https://doi.org/10.1007/BF00569651
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DOI: https://doi.org/10.1007/BF00569651