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Transmitter/Receptor Mechanisms in Cardiovascular Control by the NTS: Excitatory Amino Acids, Acetylcholine, and Substance P
Published in I. Robin A. Barraco, Nucleus of the Solitary Tract, 2019
Microinjections of AP-7 in doses specific for blocking NMDA receptors (100 pmol/20 nl) into the NTS site did not block the responses to the right atrial injection of phenylbiguanide, suggesting that specific blockade of NMDA receptors in NTS does not block the responses to cardiopulmonary vagal afferent stimulation. At higher doses, AP-7 lost its specificity for NMDA receptors. For example, 500 to 1000 pmol of AP-7 blocked the responses to microinjections of KA (3 pmol) at the same site. Even at these doses, AP-7 did not block the responses to right atrial injections of phenylbiguanide, suggesting that blockade of NMDA as well as KA receptors in the NTS is not sufficient to block the responses to cardiopulmonary receptor stimulation. Microinjections of low doses of DNQX (10 pmol/2 nl) into the NTS blocked the responses to KA (3 pmol) and AMPA (5 pmol) but failed to block the responses to right atrial injections of phenylbiguanide. A higher dose of DNQX (1000 pmol/20 nl) blocked the responses to cardiopulmonary receptor stimulation (Figure 4).
The Genetically Epilepsy-Prone Rat: Neuronal Networks And Actions Of Amino Acid Neurotransmitters
Published in Carl L. Faingold, Gerhard H. Fromm, Drugs for Control of Epilepsy:, 2019
Carl L. Faingold, Dean K. Naritoku
During AGS the levels of aspartate in the IC and glutamate in the RF of the GEPR are increased,79 and an increase in aspartate release from the hippocampus in the GEPR also is reported.94 Inter-ictally, glutamate in ICc also is reported to be elevated in one study77 but not another study of the entire IC.79 Systemic administration or microinjection into the IC of an EAA receptor antagonist, AP7 (2-amino-7-phosphonoheptanoate) or CPP (3-(( + )-2-carboxypiperazin-4-yl)-propyl-l-phosphonate) produces a significant decline in AGS severity in GEPR.31,34 Microinjection of a non-NMDA antagonist, CNQX (6-cyano-7-nitroquinox-aline-2,3-dione), or a noncompetitive NMDA antagonist, dizocilpine (MK-801) into the IC also reduces seizure severity or completely blocks seizure susceptibility in the GEPR-9.35,38 However, the competitive NMDA antagonists, CPP and AP7, are considerably more potent than the non-NMDA antagonist, CNQX. The noncompetitive NMDA antagonist, MK-801, is considerably less potent than would be expected, based on its potency when given sys-temically. MK-801 actually appears to be more effective when injected into the reticular formation (RF).35 Preliminary studies on the effects of systemically administered EAA antagonists indicate that, while CPP and AP7 reduce ICc neuronal responses, MK-801 produces a significantly smaller degree of ICc neuronal firing reduction.35a These data may suggest that MK-801 does not exert a major part of its effect on the auditory pathway, while the competitive antagonists produce extensive effects there. As noted above, microinjection of an EAA, NMDA, into the IC of normal rats renders them susceptible to AGS.25 Microinjection of AP7 or CPP into the hippocampus or amygdala in considerably higher doses does not affect AGS susceptibility or severity.15,34 Microinjection into the IC of L-canaline, which inhibits glutamate synthesis, produces a long-lasting blockade of seizure susceptibility in preliminary studies in the GEPR-933. L-Canaline pretreatment of IC slices from the GEPR significantly reduces glutamate release by potassium depolarization.83 Microinfusion into the IC of the EAA antagonists, AP7 and CNQX, blocked AGS in rats undergoing ethanol withdrawal, and the potency of AP7 is considerably greater than CNQX, as it is in the GEPR-9.38,40
Examination of sulfonamide-based inhibitors of MMP3 using the conditioned media of invasive glioma cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Alisha T. Poole, Christopher A. Sitko, Caitlin Le, Christian C. Naus, Bryan M. Hill, Eric A. C. Bushnell, Vincent C. Chen
Figure 3 shows the placement of AP-3, AP-6, AP-7 and ilomastat in the binding site of MMP3. From Table 1AP-3, AP-6, AP-7 and ilomastat all had predicted Gibbs binding energies more negative than −10 kcal mol−1. In all cases the ZBG of each compound is ligated to the Zn2+ ion, however the longer ZBG of AP-6 and AP-7 results in a different binding mode between ligand and MMP3 than seen for ilomastat. From Figure 3 the imidazole functional group of ilomastat is located in a lipophilic region which is a favourable interaction. For AP-6 and AP-7 the leucine side chain is, however, located in this region. For AP-6 and AP-7 the imidazole ring is instead located in a different lipophilic region. In the case of AP-3 it can be seen that neither the imidazole nor the leucine side chain is located in a lipophilic region providing some understanding of its weaker Gibbs binding energy (Table 1). Figures S3 and S4 show another perspective of the binding of AP-3, AP-6, AP-7 and ilomastat to MMP3.