Use of NK1 receptor antagonists in the exploration of physiological functions of substance P and neurokinin A

1995 ◽  
Vol 73 (7) ◽  
pp. 903-907 ◽  
Author(s):  
M. Qtsuka ◽  
K. Yoshioka ◽  
M. Yanagisawa ◽  
H. Suzuki ◽  
F.-Y. Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Substance P ◽  
Guinea Pig ◽  
Saphenous Nerve ◽  
Ventral Root ◽  
Neonatal Rat ◽  
Neurokinin A ◽  
Receptor Antagonists ◽  
Stimulation Of

Tachykinin NK1 receptor antagonists were used to explore the physiological functions of substance P (SP) and neurokinin A (NKA). Pharmacological profiles of three NK1 receptor antagonists, GR71251, GR82334, and RP 67580, were examined in the isolated spinal cord preparation of the neonatal rat. These tachykinin receptor antagonists exhibited considerable specificities and antagonized the actions of both SP and NKA to induce the depolarization of ventral roots. Electrical stimulation of the saphenous nerve with C-fiber strength evoked a depolarization lasting about 30 s of the ipsilateral L3 ventral root. This response, which is referred to as saphenous-nerve-evoked slow ventral root potential (VRP), was depressed by these NK1 receptor antagonists. In contrast, the saphenous-nerve-evoked slow VRP was potentiated by application of a mixture of peptidase inhibitors, including thiorphan, actinonin, and captopril in the presence of naloxone, but not after further addition of GR71251. Likewise, in the isolated coeliac ganglion of the guinea pig, electrical stimulation of the mesenteric nerves evoked in some ganglionic cells slow excitatory postsynaptic potentials (EPSPs), which were depressed by GR71251 and potentiated by peptidase inhibitors. These results further support the notion that SP and NKA serve as neurotransmitters producing slow EPSPs in the neonatal rat spinal cord and guinea pig prevertebral ganglia.Key words: substance P, neurokinin A, neurotransmitter, tachykinin antagonist, spinal cord.

Micturition reflexes in the in vitro neonatal rat brain stem-spinal cord-bladder preparation

1994 ◽  
Vol 266 (3) ◽  
pp. R658-R667 ◽  
Author(s):  
K. Sugaya ◽  
W. C. De Groat
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Brain Stem ◽  
Rat Brain ◽  
Bladder Wall ◽  
Spinal Reflex ◽  
Neonatal Rat ◽  
Evoked Contractions ◽  
Stimulation Of

An in vitro neonatal (1-7 day) rat brain stem-spinal cord-bladder (BSB) preparation was used to examine the central control of micturition. Isovolumetric bladder contractions occurred spontaneously or were induced by electrical stimulation of the ventrolateral brain stem, spinal cord, bladder wall (ES-BW), or by perineal tactile stimulation (PS). Transection of the spinal cord at the L1 segment increased the amplitude of ES-BW- and PS-evoked contractions, and subsequent removal of the spinal cord further increased spontaneous and ES-BW-evoked contractions but abolished PS-evoked contractions. Hexamethonium (1 mM), a ganglionic blocking agent, mimicked the effect of cord extirpation. Tetrodotoxin (1 microM) blocked ES-BW- and PS-evoked contractions but enhanced spontaneous contractions. Bicuculline methiodide (10-50 microM), a gamma-aminobutyric acid A receptor antagonist, increased the amplitude of spontaneous, ES-BW- and PS-evoked contractions. These results indicate that PS-evoked contractions are mediated by spinal reflex pathways, whereas spontaneous and ES-BW-evoked contractions that are elicited by peripheral mechanisms are subject to a tonic inhibition dependent on an efferent outflow from the spinal cord. PS-evoked micturition is also subject to inhibitory modulation arising from sites rostral to the lumbosacral spinal cord. Although electrical stimulation of bulbospinal excitatory pathways can initiate bladder contractions in the neonatal rat, these pathways do not appear to have an important role in controlling micturition during the first postnatal week.

scholarly journals Flexibility of Motor Pattern Generation Across Stimulation Conditions by the Neonatal Rat Spinal Cord

2010 ◽  
Vol 103 (3) ◽  
pp. 1580-1590 ◽  
Author(s):  
David A. Klein ◽  
Angelica Patino ◽  
Matthew C. Tresch
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Muscle Activation ◽  
Motor Pattern ◽  
Pattern Generation ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Afferent Pathways ◽  
Motor Pattern Generation ◽  
Stimulation Of

Previous studies have demonstrated that “locomotor-like” rhythmic patterns can be evoked in the isolated neonatal rat spinal cord by several means, including pharmacological neuromodulation and electrical stimulation of various pathways. Recent studies have used stimulation of afferent pathways to evoke rhythmic patterns, relying on synaptic activation of interneuronal systems rather than global imposition of neuromodulatory state by pharmacological agents. We use the in vitro neonatal rat spinal cord with attached hindlimb to examine the muscle activation patterns evoked by stimulation of these different pathways and evaluate whether stimulation of these pathways all evoke the same patterns. We find that the patterns evoked by bath application of serotonin (5-HT) and N-methyl-d-aspartic acid (NMDA) consisted of alternation between hip flexors and extensors and similar alternation was observed in the patterns evoked by electrical stimulation of the cauda equina (CE) or contralateral fifth lumbar (L5) dorsal nerve root. In contrast, the knee extensor/hip flexor rectus femoris (RF) and knee flexor/hip extensor semitendinosus (ST) were activated differentially across stimulation conditions. In 5-HT/NMDA patterns, RF was active in late flexion and ST in late extension. In CE patterns, these two muscles switched places with RF typically active in late extension and ST active in flexion. In L5 patterns, ST was activated in extension and RF was silent or weakly active during flexion. There were also systematic differences in the consistency of rhythms evoked by each stimulation method: patterns evoked by electrical stimulation of CE or L5 were less consistently modulated with the rhythm when compared with 5-HT/NMDA-evoked patterns. All differences were preserved following deafferentation, demonstrating that they reflect intrinsic properties of spinal systems. These results highlight the intrinsic flexibility of motor pattern generation by spinal motor circuitry which is present from birth and provides important information to many studies examining spinal pattern generating networks.

Capsaicin induced release of multiple tachykinins (substance P, neurokinin A and eledoisin-like material) from guinea-pig spinal cord and ureter

Neuroscience ◽  
1986 ◽  
Vol 19 (1) ◽  
pp. 313-319 ◽  
Author(s):  
X.-Y. Hua ◽  
A. Saria ◽  
R. Gamse ◽  
E. Theodorsson-Norheim ◽  
E. Brodin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Guinea Pig ◽  
Neurokinin A

Characteristics of electrically induced locomotion in rat in vitro brain stem-spinal cord preparation

1990 ◽  
Vol 64 (3) ◽  
pp. 727-735 ◽  
Author(s):  
Y. Atsuta ◽  
E. Garcia-Rill ◽  
R. D. Skinner
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Brain Stem ◽  
Neonatal Rat ◽  
Step Cycle ◽  
Cycle Frequency ◽  
Adult Rat ◽  
Pattern Generators ◽  
Stimulation Of

1. Electrical stimulation of two brain stem regions in the decerebrate neonatal rat brain--the mesencephalic locomotor region (MLR) and the medioventral medulla (MED)--were found to elicit rhythmic limb movements in the hind-limb-attached, in vitro, brain stem-spinal cord preparation. 2. Electromyographic (EMG) analysis revealed locomotion similar to that observed during stepping in the adult rat. The step-cycle frequency could be increased by application of higher-amplitude currents; but, unlike the adult, alternation could not be driven to a gallop. 3. Threshold currents for inducing locomotion were significantly lower for stimulation of the MED compared with the MLR. Brain stem transections carried out at midpontine levels demonstrated that the presence of the MLR was not required for the expression of MED-stimulation-induced effects. 4. Substitution of the standard artificial cerebrospinal fluid (aCSF) by magnesium-free aCSF did not affect interlimb relationships and resulted in a significant decrease of the threshold currents for inducing locomotion. 5. Fixation of the limbs during electrical stimulation of brain stem sites altered the amplitude and duration of the EMG patterns, but the basic rhythm and timing of each muscle contraction during the step cycle was not affected. 6. These studies suggest that, although peripheral afferent modulation is evident in the neonatal locomotor control system, descending projections from brain stem-locomotor regions appear capable of modulating the activity of spinal pattern generators as early as the day of birth. However, there may be ceiling to the maximal frequency of stepping possible at this early age, perhaps suggesting a later-developing mechanism for galloping.

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