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Sakurada, T. et al.

Naloxone-reversible effect of spantide on the spinally mediated behavioural response induced by neurokinin-2 and -3 receptor agonists.

[D-Arg1, D-Trp7,9, Leu11]-substance P (spantide) was tested for antagonism against the licking, biting and scratching response induced by various neurokinin (NK) receptor agonists and bombesin (Bom) in mice. When co-administered with substance P ( SP) intrathecally, spantide reduced the SP-induced behavioural responses in a dose-dependent manner. The duration of this antagonistic effect was approximately 30 min. Behavioural responses induced by physalaemin (Phy), [pGlu6, L-Pro9]-SP (6-11) (septide), [pGlu6, D-Pro7]-SP (6-11) (D-septide) and eledoisin (Ele) were also dose-dependently decreased by relatively small doses of spantide. Higher doses of spantide were needed to reduce the behavioural responses induced by [Sar9, Met (O2)11]-SP, neurokinin A ( NK A) and neurokinin B (NK B). No significant effect of spantide was observed against the behavioural responses elicited by Bom. Pretreatment with naloxone, an opioid antagonist, resulted in a reversible effect on the behavioural reduction of NK-2 and NK-3 receptor agonists produced by spantide. However, the effect of spantide on the NK-1 receptor agonist-induced response was unchanged by naloxone. In homogenates of mouse spinal cord, competition studies confirmed that the binding of the opioid ligand [3H]naloxone was displaced by spantide with a low but measurable affinity. These results suggest that the behavioural response to NK-2 and NK-3 receptor agonists may be partially inhibited by spantide through the activation of opioid system in the mouse spinal cord.[1]

References

Naloxone-reversible effect of spantide on the spinally mediated behavioural response induced by neurokinin-2 and -3 receptor agonists. Sakurada, T., Manome, Y., Katsumata, K., Uchiumi, H., Tan-No, K., Sakurada, S., Kisara, K. Naunyn Schmiedebergs Arch. Pharmacol. (1992) [Pubmed]

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