title: An NK1 receptor-dependent component of the slow excitation recorded intracellularly from rat motoneurons following dorsal root stimulation.
abstract: Intracellular recording from lumbar motoneurons of the neonatal rat spinal cord in vitro was used to study how recently developed non-peptide antagonists such as SR-140333 and SR-48698, known to block distinct subtypes of tachykinin receptors peripherally, might affect synaptic transmission elicited by electrical stimulation of dorsal root fibres. SR-140333 (1 microM) preferentially antagonized responses mediated by an exogenously applied agonist acting on the NK1 receptor subclass, while SR-48968 (0.5 microM) preferentially reduced responses mediated by an exogenously applied agonist acting on the NK2 receptor subclass. SR-48968 did not affect fast or slow excitatory postsynaptic potentials (EPSPs) or 'wind-up' responses induced by repetitive, low-frequency stimulation (mimicking certain types of nociceptive input); binding studies using this radiolabelled ligand disclosed specific binding activity (21 fmol/mg protein) selectively displaced by an NK2 receptor agonist. SR-140333 reduced the late component of fast and slow EPSPs, and of wind-up. Pharmacological block of ionotropic glutamate receptors abolished all dorsal root-evoked EPSPs. In comparison to glutamate receptor blockers, SR-140333 was a weaker antagonist of slow synaptic responses, though it displayed preferential antagonism towards some components of the wind-up phenomenon. The present results provide evidence obtained with a novel NK1 antagonist that a neuropeptide (presumably substance P), although not directly released by primary afferents onto motoneurons, is a neurotransmitter (acting via NK1 receptors) in the pathway mediating slow synaptic responses of motoneurons, and is presumably involved in signalling nociceptive inputs from the periphery.
authors.affiliation: International School for Advanced Studies (S.I.S.S.A.), Trieste, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Baranauskas
authors.forename: U
authors.initials: U
authors.lastname: Traversa
authors.forename: A M
authors.initials: AM
authors.lastname: Rosati
authors.forename: A
authors.initials: A
authors.lastname: Nistri
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D018039:Receptors, Tachykinin / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology
chemical_list: D001549:Benzamides; D010880:Piperidines; D011812:Quinuclidines; D018039:Receptors, Tachykinin; C085215:SR 140333; C073839:SR 48968