Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interaction between neurokinin and excitatory amino acid receptors in the spinal cord have been characterised using the neonatal rat spinal cord in vitro preparation. Ventral root (VR) depolarization evoked by N-methyl-D-aspartate (NMDA) and quisqualate was reversibly enhanced in the presence of subthreshold concentrations of neurokinin A (NKA; 1.0-10 nM), but not by substance P (1.0-5.0 nM). When substance P (SP) was replaced by the metabolically stable substance P methyl ester (SPOMe), both NMDA and quisqualate responses were significantly enhanced. VR depolarization evoked by kainate was not altered by any of the neurokinin (NK) receptor agonists. In the presence of the endopeptidase inhibitors, bestatin, captopril and thiorphan (each 1.0 microM), SP significantly enhanced NMDA-evoked responses. The selective NK1 receptor antagonist (+/-) CP96 345 (100 nM) reversibly blocked the enhancement of NMDA-evoked depolarization by SPOMe. Furthermore, MEN10 376 (50 nM), a selective NK2 receptor antagonist blocked the enhancement of NMDA- and quisqualate-evoked depolarization by NKA. The protein kinase C and protein kinase A inhibitor staurosporine (1.0 microM) blocked the enhancement of excitatory amino acid-induced responses by NK-receptor activation. However, whilst NKA-evoked ventral root depolarization was completely abolished in the presence of staurosporine, SPOMe- and SP-induced depolarizations were unaffected. These data show that activation of NK1 or NK2 receptors enhances NMDA- and quisqualate-evoked ventral root depolarization in the neonatal rat spinal cord. The interaction between neurokinin and excitatory amino acid receptors involves protein kinase C activation.
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PMID:Tachykinin induced regulation of excitatory amino acid responses in the rat spinal cord in vitro. 751 61

The effects of sensory neuropeptides on the airway responsiveness to acetylcholine (ACh) were investigated in normal nonsensitized rats. The airway responsiveness to inhaled ACh was significantly increased after treatment with neurokinin A (NKA; 0.001%) or substance P (SP; 0.01%) aerosol in the presence of the neutral endopeptidase (NEP) inhibitor. NKA had a more potent effect than SP. Interestingly, the intravenous treatment with NEP inhibitor alone also induced airway hyperresponsiveness (AHR) to inhaled ACh. This AHR was significantly attenuated by pretreatment with a nonselective NK-receptor antagonist, [D-Pro2,D-Trp7,9]SP, systemic capsaicin, or bilateral cervical vagotomy, indicating that decreased NEP activity results in accumulation of endogenous sensory neuropeptide(s) and enhancement of vagal reflex to cause AHR. The airway responsiveness to ACh of isolated left main bronchus was also increased after treatment with 10(-6) M NKA, but not SP, together with 10(-6) M phosphoramidon. This in vitro AHR to ACh induced by phosphoramidon plus NKA was significantly attenuated by pretreatment with 10(-6) M tetrodotoxin. These findings suggest that overaccumulated sensory neuropeptides, especially NKA, may enhance the probability of transmitter release, probably via NK2 receptors, and that the enhanced transmitter release might be involved in AHR in rats.
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PMID:Inhibition of neutral endopeptidase increases airway responsiveness to ACh in nonsensitized normal rats. 753 95