Characterization of tachykinin-induced ventral root depolarization in the neonatal rat isolated spinal cord.
Depolarization responses to tachykinin receptor agonists were recorded extracellularly from lumbar ventral roots of spinal cord isolated from neonatal rats (one to eight days post partum). All spinal cords were hemisected in the sagittal plane. In addition, in some hemisected cords, the dorsal horns were removed by means of a further cut, perpendicular to the first. In both hemisected and quadrisected spinal cords, reproducible depolarization responses were induced by low concentrations of the neurokinin-1-selective agonist substance P methylester (10 nM-1 microM) or of the neurokinin-3-selective agonist senktide (3-300 nM). On both types of preparation, responses to substance P methylester (1 microM) or senktide (300 nM) were of comparable size. The amplitude of the response to senktide (300 nM) was reduced by at least 88% in spinal cord preparations exposed to tetrodotoxin (0.5 microM) or to physiological medium containing magnesium chloride (20 mM). In contrast, under either of these conditions, concentration-response curves to substance P methylester were shifted rightward by 2.8-8.5-fold, with little effect on the maximum response. Responses to senktide were blocked selectively by the N-methyl-D-aspartate antagonist 3-[(+-)-2-carboxypiperazine-4-yl]propyl-1-phosphonic acid (100 microM); the antagonist had little effect on substance P methylester-induced depolarization (mean concentration ratio 2.0). These results suggest that in the neonatal rat spinal cord, application of exogenous tachykinin agonists can induce ventral root depolarization by activation of neurokinin-1 and/or neurokinin-3 receptors. The response to stimulation of neurokinin-1 receptors has a major component likely to be due to a direct action at motoneurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Ireland
S J
SJ
Department of Neuropharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, U.K.
Wright
I K
IK
Jordan
C C
CC
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D015636:Magnesium Chloride / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013126:Spinal Nerve Roots / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D009467:Neuromuscular Depolarizing Agents; D010446:Peptide Fragments; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; D015636:Magnesium Chloride; C054724:senktide; D013373:Substance P; D013779:Tetrodotoxin; C033611:substance P, methyl ester-; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid