MULTIPLE TYPES OF TACHYKININ RECEPTOR MEDIATE A SLOW EXCITATION OF RAT SPINAL MOTONEURONS IN-VITRO

Using intracellular current clamp recording from motoneurones of the neonatal rat spinal cord in vitro, the action of tachykinin receptor agonists was investigated. Test drugs included the endogenously occurring neuropeptide substance P and synthetic compounds, such as substance P methylester (SPMeO), [beta Ala(8)]neurokinin A(4-10) ([Ala]NKA), [MePhe(7)]neurokinin B ([MePhe]NKB) and senktide. SPMeO and [Ala]NKA were used as selective agonists at NK1 and NK2 receptors, respectively, while [MePhe]NKB or senktide were employed to activate NK3 receptors. In control solution, all compounds produced sustained depolarization with increase in input resistance although at comparable levels of membrane depolarization different patterns of motoneuronal firing were observed dependent on the type of agonist tested. In tetrodotoxin (TTX; 1 mu M) solution, the depolarization caused by substance P or SPMeO largely persisted while in the majority of cells the effect of [Ala]NKA, [MePhe]NKB or senktide was blocked. It is suggested that NK1 receptors primarily mediated the actions of substance P on spinal motoneurones and that activation of NK2 or NK3 receptors, predominantly found on interneurones, induced motoneuronal depolarization with different firing patterns.