PHYSIOLOGICAL AND PHARMACOLOGICAL CHARACTERIZATION OF THE SPINAL TACHYKININ NK2 RECEPTOR

The goal of these investigations was to study the role of tachykinin N K2 receptors in neonatal spinal cords using the selective NK2 receptor agonist [beta-Ala(8)]neurokinin A-(4-10) and the new NK2 receptor ant agonist GR 94800. Experiments were performed with superfused hemisecte d rat and gerbil spinal cords. Dorsal roots were electrically stimulat ed and the synaptically elicited responses and the DC-potentials were recorded extracellularly from the corresponding ventral roots. [beta-A la(8)]neurokinin A-(4-10) depolarized ventral roots (0.01-10 mu M) and increased their spontaneous activity in a concentration-dependent man ner. These effects of [beta-Ala(8)]neurokinin A-(4-10) were reduced by GR 94800. The action of GR 94800 was selective because the depolarizi ng effects of similar magnitude evoked by the NK1 receptor agonist [Sa r(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 NK2 receptor agonist was more potent in the rat th an in the gerbil. The estimated EC(50) (means +/- S.E.M) was found to be 3.9 +/- 6.0/-1.3 mu M in the rat and 2.4 + 2.9/-1.3 mu M in the ger bil spinal cord. The NK2 receptor agonist [beta-Ala(8)]neurokinin A-(4 -10) potentiated the monosynaptic reflex evoked by dorsal root stimula tion. The potentiation manifested itself as an increase in the amplitu de 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 mu M), respectively. Tetrodotoxi n reduced the depolarizing action elicited by the NK2 receptor agonist , suggesting that part of the [beta-Ala(8)]neurokinin A-(4-10) effect is probably located presynaptically. In contrast to the NK1 receptor a ntagonist (+/-)-CP-96,345, the NK2 receptor antagonist GR 94800 showed no species differences. In conclusion, NK2 receptors appear to have a physiological role in regulating spinal neuronal activity.