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

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Summary

[d-Arg1, dTrp7,9, 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.

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Authors and Affiliations

  1. Department of Pharmacology, Tohoku College of Pharmacy, 4-4-1 Komatsushima, 981, Aoba-ku, Sendai, Japan

    T. Sakurada, Y. Manome, K. Katsumata, H. Uchiumi, K. Tan-No, S. Sakurada & K. Kisara

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  1. T. Sakurada
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  2. Y. Manome
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  3. K. Katsumata
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  4. H. Uchiumi
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  5. K. Tan-No
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  6. S. Sakurada
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  7. K. Kisara
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Sakurada, T., Manome, Y., Katsumata, K. et al. Naloxone-reversible effect of spantide on the spinally mediated behavioural response induced by neurokinin-2 and -3 receptor agonists. Naunyn-Schmiedeberg's Arch Pharmacol 346, 69–75 (1992). https://doi.org/10.1007/BF00167573

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  • DOI: https://doi.org/10.1007/BF00167573

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