TACHYKININ-INDUCED REGULATION OF EXCITATORY AMINO-ACID RESPONSES IN THE RAT SPINAL-CORD IN-VITRO

The interaction between neurokinin and excitatory amino acid receptors in the spinal cord have been characterised using the neonatal rat spi nal cord in vitro preparation. Ventral root (VR) depolarization evoked by N-methyl-D-aspartate (NMDA) and quisqualate was reversibly enhance d in the presence of subthreshold concentrations of neurokinin A (NKA; 1.0-10 nM), but not by substance P (1.0-5.0 nM). When substance P (SP ) was replaced by the metabolically stable substance P methyl ester (S POMe), both NMDA and quisqualate responses were significantly enhanced . VR depolarization evoked by kainate was not altered by any of the ne urokinin (NK) receptor agonists. In the presence of the endopeptidase inhibitors, bestatin, captopril and thiorphan (each 1.0 mu M), SP sign ificantly enhanced NMDA-evoked responses. The selective NK1 receptor a ntagonist (+/-) CP96 345 (100 nM) reversibly blocked the enhancement o f NMDA-evoked depolarization by SPOMe. Furthermore, MEN10 376 (50 nM), a selective NK2 receptor antagonist blocked the enhancement of NMDA- and quisqualate-evoked depolarization by NKA. The protein kinase C and protein kinase A inhibitor staurosporine (1.0 mu M) blocked the enhan cement of excitatory amino acid-induced responses by NK-receptor activ ation. However, whilst NKA-evoked ventral root depolarization were una ffected. These data show that activation of NK1 or NK2 receptors enhan ces NMDA- and quisqualate-evoked ventral root depolarization in the ne onatal rat spinal cord. The interaction between neurokinin and excitat ory amino acid receptors involves protein kinase C activation.