Modulation of excitatory amino acid responses in rat dorsal horn neurons by tachykinins

1992 ◽  
Vol 68 (1) ◽  
pp. 265-286 ◽  
Author(s):  
K. I. Rusin ◽  
P. D. Ryu ◽  
M. Randic
Keyword(s):  
Steady State ◽  
Substance P ◽  
Dorsal Horn ◽  
Peak Amplitude ◽  
Neurokinin A ◽  
Induced Current ◽  
Simultaneous Application ◽  
Transient Component ◽  
Nmda Current ◽  
State Component

1. In freshly isolated spinal dorsal horn (DH) neurons (laminae I-III) of the young rat, the effects of tachykinins (substance P, neurokinin A) on inward current induced by excitatory amino acids were studied under whole-cell voltage-clamp conditions. 2. When the cells were clamped to a holding potential of -60 mV, a simultaneous application of N-methyl-D-aspartate (NMDA) (10(-4) M) and substance P (SP) (2 x 10(-9)-10(-7) M) for 10 s reversibly enhanced (by 129.6 +/- 8.2%, mean +/- SE) the peak amplitude of the initial transient component of the NMDA-induced current in approximately 60% of the examined cells and reduced it (to 83.3 +/- 2.7%) in 27% of the cells. In addition, SP produced an increase (by 133.6 +/- 11.7%) or a small decrease (to 85.9 +/- 1.4%) in the steady-state component of the NMDA response. In difference to SP, a simultaneous application of NMDA (10(-4) M) and neurokinin A (NKA) (10(-10)-10(-7) M) reversibly suppressed (to 86.8 +/- 2.1%) the peak amplitude of the NMDA-induced current in 75% of the examined cells. 3. The NMDA-induced currents were modulated by tachykinins not only during the coadministration but up to 20 min after the removal of the peptide. SP potentiated the initial peak NMDA current by 147.9 +/- 8.1% in 78% of examined cells and decreased it (76.3 +/- 5.7%) in 11% of cells. The potentiating effect was concentration-dependent (range: 10(-11)-10(-8) M) and reversible, but it was reduced with repeated applications. In addition, SP increased (by 125.4 +/- 3.6%) or reduced (to 86.0 +/- 1.8%) the steady-state component of the NMDA response. 4. When the single DH neurons were exposed to SP or NKA for 30 s-7 min before the testing of the NMDA responses, tachykinins had two distinct effects on the peak amplitude of the transient component of the NMDA-induced current, consisting of an initial depression (SP: to 64.8 +/- 2.1%; NKA: to 76.3 +/- 4.4%) followed by a potentiation (SP: by 146.6 +/- 6.8%; NKA: by 178.4 +/- 35.2%). The enhancing effect in some cells lasted less than or equal to 1 h. 5. A claimed novel nonselective tachykinin antagonist, spantide II (10(-8) M) coadministered with NMDA (10(-4) M), slightly depressed the peak component of NMDA-induced current. In addition, it effectively blocked the SP-induced potentiation of the responses of DH neurons to NMDA.(ABSTRACT TRUNCATED AT 400 WORDS)

Attenuation of reflex pressor and ventilatory responses to static contraction by an NK-1 receptor antagonist

1992 ◽  
Vol 73 (4) ◽  
pp. 1389-1395 ◽  
Author(s):  
J. M. Hill ◽  
J. G. Pickar ◽  
M. P. Kaufman
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Intrathecal Injection ◽  
Muscular Contraction ◽  
Muscle Afferents ◽  
Neurokinin A ◽  
Ventilatory Responses ◽  
Static Contraction

The chemical messengers released onto second-order dorsal horn neurons from the spinal terminals of contraction-activated group III and IV muscle afferents have not been identified. One candidate is the tachykinin substance P. Related to substance P are two other tachykinins, neurokinin A (NKA) and neurokinin B (NKB), which, like substance P, have been isolated in the dorsal horn of the spinal cord and have receptors there. Whether NKA or NKB plays a transmitter/modulator role in the spinal processing of the exercise pressor reflex is unknown. Therefore, we tested the following hypotheses. After the intrathecal injection of a highly selective NK-1 (substance P) receptor antagonist onto the lumbosacral spinal cord, the reflex pressor and ventilatory responses to static muscular contraction will be attenuated. Likewise, after the intrathecal injection either of an NK-2 (NKA) receptor antagonist or an NK-3 (NKB) receptor antagonist onto the lumbrosacral spinal cord, the reflex pressor and ventilatory responses to static contraction will be attenuated. We found that, 10 min after the intrathecal injection of 100 micrograms of the NK-1 receptor antagonist, the pressor and ventilatory responses to contraction were significantly (P < 0.05) attenuated. Mean arterial pressure was attenuated by 13 +/- 3 mmHg (48%) and minute volume of ventilation by 120 +/- 38 ml/min (34%). The cardiovascular and ventilatory responses to contraction before either 100 micrograms of the NK-2 receptor antagonist or 100 micrograms of the NK-3 receptor antagonist were not different (P > 0.05) from those after the NK-2 or the NK-3 receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals cDNA sequence of human β-preprotachykinin, the common precursor to substance P and neurokinin A

FEBS Letters ◽  
1986 ◽  
Vol 208 (1) ◽  
pp. 67-72 ◽  
Author(s):  
A.J. Harmar ◽  
A. Armstrong ◽  
J.C. Pascall ◽  
K. Chapman ◽  
R. Rosie ◽  
...  
Keyword(s):  
Substance P ◽  
Cdna Sequence ◽  
Neurokinin A ◽  
Common Precursor ◽  
The Common

Distribution of substance P in the spinal cord of patients with syringomyelia

1996 ◽  
Vol 84 (6) ◽  
pp. 992-998 ◽  
Author(s):  
Thomas H. Milhorat ◽  
Harrison T. M. Mu ◽  
Carole C. LaMotte ◽  
Ade T. Milhorat
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Dorsal Horn ◽  
Ventral Horn ◽  
Immunohistochemical Method ◽  
Positive Staining ◽  
Content Type ◽  
Normal Individuals ◽  
Neurologically Normal ◽  
Intermediolateral Nucleus

✓ The distribution of substance P, a putative neurotransmitter and pain-related peptide, was studied using the peroxidase—antiperoxidase immunohistochemical method in the spinal cords obtained from autopsy of 10 patients with syringomyelia and 10 age- and sex-matched, neurologically normal individuals. Substance P immunoreactivity was present in axons and in terminal-like processes in close apposition to neurons in the first, second, and third laminae of the dorsal horn. Smaller amounts of peroxidase-positive staining were found in the fifth lamina of the dorsal horn, the intermediolateral nucleus, the intermediomedial nucleus, and the ventral horn. In nine of 10 patients with syringomyelia, there was a substantial increase in substance P immunoreactivity in the first, second, third, and fifth laminae below the level of the lesion. A marked reduction or absence of staining was present in segments of the spinal cord occupied by the syrinx. Central cavities produced bilateral abnormalities, whereas eccentric cavities produced changes that were ipsilateral to the lesion. No alterations in staining were found in the spinal cord of an asymptomatic patient with a small central syrinx. The authors conclude that syringomyelia can be associated with abnormalities in spinal cord levels of substance P, which may affect the modulation and perception of pain.

Tachykinins (Substance P, Neurokinin A and Neuropeptide γ) and Neurotensin from the Intestine of the Burmese Python, Python molurus

Peptides ◽  
1997 ◽  
Vol 18 (10) ◽  
pp. 1505-1510 ◽  
Author(s):  
J.Michael Conlon ◽  
Thomas E Adrian ◽  
Stephen M Secor
Keyword(s):  
Substance P ◽  
Neurokinin A ◽  
Python Molurus

Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs

1992 ◽  
Vol 73 (5) ◽  
pp. 1847-1853 ◽  
Author(s):  
S. A. Shore ◽  
M. A. Martins ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Ace Inhibitor ◽  
Dynamic Compliance ◽  
Neutral Endopeptidase ◽  
Neurokinin A ◽  
Mechanically Ventilated ◽  
Arterial Blood ◽  
Airway Responses ◽  
Nep Inhibition

We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.

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