Physiological and pharmacological characterization of the spinal tachykinin NK2 receptor.

Abstract The goal of these investigations was to study the role of tachykinin NK 2 receptors in neonatal spinal cords using the selective NK 2 receptor agonist [β-Ala 8 ]neurokinin A-(4–10) and the new NK 2 receptor antagonist GR 94800. Experiments were performed with superfused hemisected rat and gerbil spinal cords. Dorsal roots were electrically stimulated and the synaptically elicited responses and the DC-potentials were recorded extracellularly from the corresponding ventral roots. [β-Ala 8 ]neurokinin A-(4–10) depolarized ventral roots (0.01–10 μM) and increased their spontaneous activity in a concentration-dependent manner. These effects of [β-Ala 8 ]neurokinin A-(4–10) were reduced by GR 94800. The action of GR 94800 was selective because the depolarizing effects of similar magnitude evoked by the NK 1 receptor agonist [Sar 9 , Met(O 2 ) 11 ]substance P were not affected by GR 94800. The pA 2 values of GR 94800 amounted to 6.0±0.4 in the rat and 5.4±0.3 in the gerbil. The NK 2 receptor agonist was more potent in the rat than in the gerbil. The estimated EC 50 (means ± S.E.M.) was found to be 3.9 + 6.0/ − 1.3 μM in the rat and 2.4 + 2.9/ − 1.3 μM in the gerbil spinal cord. The NK 2 receptor agonist [β-Ala 8 ]neurokinin A-(4–10) potentiated the monosynaptic reflex evoked by dorsal root stimulation. The potentiation manifested itself as an increase in the amplitude of the early component of the response. The receptor type mediating this effect could not be elucidated. The potentiation ranged between 30 ± 27 and 110 ± 36% (0.3 and 10 μM), respectively. Tetrodotoxin reduced the depolarizing action elicited by the NK 2 receptor agonist, suggesting that part of the [β-Ala 8 ]neurokinin A-(4–10) effect is probably located presynaptically. In contrast to the NK 1 receptor antagonist (±)-CP-96,345, the NK 2 receptor anatgonist GR 94800 showed no species differences. In conclusion, NK 2 receptors appear to have a physiological role in regulating spinal neuronal activity.