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.
Sakurada
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Manome
Y
Y
Katsumata
K
K
Uchiumi
H
H
Tan-No
K
K
Sakurada
S
S
Kisara
K
K
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009270:Naloxone / Q000494:pharmacology*; D015288:Neurokinin A / Q000494:pharmacology; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D011957:Receptors, Opioid / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D013373:Substance P; D009270:Naloxone; D015288:Neurokinin A; C042867:spantide