Physiological and pharmacological characterization of the spinal tachykinin NK2 receptor.

The goal of these investigations was to study the role of tachykinin NK2 receptors in neonatal spinal cords using the selective NK2 receptor agonist [beta-Ala8]neurokinin A-(4-10) and the new NK2 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. [beta-Ala8]neurokinin A-(4-10) depolarized ventral roots (0.01-10 microM) and increased their spontaneous activity in a concentration-dependent manner. These effects of [beta-Ala8]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 NK1 receptor agonist [Sar9,Met(O2)11]substance P were not affected by GR 94800. The pA2 values of GR 94800 amounted to 6.0 +/- 0.4 in the rat and 5.4 +/- 0.3 in the gerbil. The NK2 receptor agonist was more potent in the rat than in the gerbil. The estimated EC50 (mean +/- S.E.M.) was found to be 3.9 + 6.0/-1.3 microM in the rat and 2.4 + 2.9/-1.3 microM in the gerbil spinal cord. The NK2 receptor agonist [beta-Ala8]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 microM), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)