Changes in preference for receptor subtypes of configurational variants of a glutamate analog: Conversion from the NMDA-type to the non-NMDA type

Ishida, Michiko; Ohfune, Yasufumi; Shimada, Yumiko; Shimamoto, Keiko; Shinozaki, H.

doi:10.1016/0006-8993(91)90420-z

Cited by 14 publications

(8 citation statements)

References 12 publications

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“…cis -MCG-IV retained the agonistic activity to NMDA receptors, while its activity was less than that of CCG-IV. To our surprise, trans -MCG-IV, which is a configurational isomer at C3‘ of cis -MCG-IV, was found to activate KA receptors (vide infra). 12a, …”

Section: Resultsmentioning

confidence: 96%

“…To our surprise, trans -MCG-IV, which is a configurational isomer at C3‘ of cis -MCG-IV, was found to activate KA receptors (vide infra). 12a, …”

Section: Resultsmentioning

confidence: 96%

“…Neurobiological Activities of MCGs. The neurobiological actions of the synthetic MCGs in the mammalian CNS were examined mainly using electrophysiological methods (Table ). ,− Both cis - and trans -MCG-I did not cause any depolarizing activities even at high concentrations (>1 mM) in the new born rat isolated spinal cord 12b,27,28 However, they potentially inhibited presynaptic neurotransmission. , Such inhibition has been known as one of the characteristic physiological actions of mGluRs . Accordingly, they were classified as potent agonists of mGluRs.…”

Section: Resultsmentioning

confidence: 99%

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Syntheses and Conformational Analyses of Glutamate Analogs: 2-(2-Carboxy-3-substituted-cyclopropyl)glycines as Useful Probes for Excitatory Amino Acid Receptors

1996

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An hypothesis that each subtype of glutamate receptors requires a specific conformation of L-glutamate for its selective activation was examined using the conformationally constrained analogs of L-glutamate, L-2-(2-carboxycyclopropyl)glycines (CCGs), and L-2-[2-carboxy-3-(methoxymethyl)cyclopropyl)glycines (MCGs). All MCG isomers were newly synthesized in a stereoselective manner via the common synthetic intermediate 5a starting with the oxazolidine aldehyde 1. The synthesis of the four MCG isomers was characterized by a stereoselective inversion of alpha-cyclopropyl acyl anion (e.g., from 10 to 11). The spectroscopic studies, in particular, pH vs J correlation experiments of CCGs and MCGs using 1H NMR and their molecular mechanics calculations, revealed that these analogs possessed an antiperiplanar conformation regarding the H-C2-C1'-H bond as a majority among the other possible rotamers in aqueous solution. The fact that each CCG and MCG exhibited potent and selective activities to the distinct types of glutamate receptors allowed us to extract an active conformation of L-glutamate. Thus, the conformational requirement of metabotropic glutamate receptors was speculated to be the anti-anti conformation (aa-A) because the conformations of CCG-1 and cis and trans-MCG-I, selective agonists of the receptors, closely mimicked the rotamer A of L-glutamate. On the other hand, N-methyl-D-aspartate and kainate receptors, representative ionotropic glutamate receptors, would require glutamate g+g+ rotamer E which was deduced from the conformation-activity relationship studies of the selective agonists CCG-IV, cis-MCG-IV, and trans-MCG-IV and the related analogs.

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Section: Resultsmentioning

confidence: 96%

“…To our surprise, trans -MCG-IV, which is a configurational isomer at C3‘ of cis -MCG-IV, was found to activate KA receptors (vide infra). 12a, …”

Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

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Syntheses and Conformational Analyses of Glutamate Analogs: 2-(2-Carboxy-3-substituted-cyclopropyl)glycines as Useful Probes for Excitatory Amino Acid Receptors

1996

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Section: Discussionmentioning

confidence: 99%

“…Some excitatory amino acids, however, that are not related structurally to kainate, including 5-bromowillardiine (Agrawal & Evans, 1986) and some derivatives of 2-(carboxycyclopropyl)glycine (CCG) , also cause considerable depolarization of the dorsal root fibre, and 5-bromowillardiine is much more potent than kainate in causing depolarization of the dorsal root fibre. Therefore, they have been regarded as kainate-type agonists (Watkins et al, 1990a;Ishida et al, 1991 (Agrawal & Evans, 1986) and the dorsal root ganglion (Huettner, 1990) while it did not occur in the spinal motoneurone. Therefore, the difference in degree of development of receptor desensitization between both preparations may play a key role for a difference in the rank order of the depolarizing activity, but the existence of different types of kainate receptors is also strongly suggested.…”

Section: Cross Desensitization Between Kainate Derivativesmentioning

confidence: 99%

Novel kainate derivatives: potent depolarizing actions on spinal motoneurones and dorsal root fibres in newborn rats

Ishida

Shinozaki²

1991

British J Pharmacology

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1Neuropharmacological actions of several kainate derivatives (kainoids) were examined for electrophysiological effects in the isolated spinal cord and the dorsal root fibre of the newborn rat. 2 Some kainoids caused depolarization of the motoneurone much more effectively than kainic acid or domoic acid and others were weaker. The rank order of the depolarizing activities of the kainoids tested here is as follows: 442-methoxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (MFPA) > acromelic acid A > domoic acid _ 4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid (HFPA) _ acromelic acid B > kainic acid. 3 In the isolated dorsal root fibre, domoic acid caused the most significant depolarization. There were distinct differences with regard to the rank order of the depolarizing activity between the motoneurone and the dorsal root fibre. The rank order in the dorsal root fibre is domoic acid > acromelic acid B > 5-bromowillardiine _ MFPA > acromelic acid A > HFPA > kainic acid. 4 Significant desensitization of kainate receptors was observed in the isolated dorsal root fibre during prolonged application of L-glutamate, kainate and its derivatives. Cross desensitization was also observed among these excitatory amino acids. Receptors desensitized by kainate did not respond to MFPA, HFPA and acromelic acids, suggesting that these kainate derivatives activated common kainate receptors in the dorsal root fibre.5 In both motoneurones and dorsal root fibres, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) effectively depressed the depolarization induced by kainoids, and neither 3-[(±)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP) nor picrotoxin blocked or affected the depolarization, but there were some differences in pharmacological potencies of glutamate antagonists between both preparations. 6 MFPA, HFPA and acromelic acids should provide valuable pharmacological tools for analysis of physiological functions of excitatory amino acids, in particular, as specific agonists for some subtypes of kainate receptors.

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Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state

Mayer

Olson

Gouaux

2001

Journal of Molecular Biology

136

115

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Changes in preference for receptor subtypes of configurational variants of a glutamate analog: Conversion from the NMDA-type to the non-NMDA type

Cited by 14 publications

References 12 publications

Syntheses and Conformational Analyses of Glutamate Analogs: 2-(2-Carboxy-3-substituted-cyclopropyl)glycines as Useful Probes for Excitatory Amino Acid Receptors

Syntheses and Conformational Analyses of Glutamate Analogs: 2-(2-Carboxy-3-substituted-cyclopropyl)glycines as Useful Probes for Excitatory Amino Acid Receptors

Novel kainate derivatives: potent depolarizing actions on spinal motoneurones and dorsal root fibres in newborn rats

Mechanisms for ligand binding to GluR0 ion channels: crystal structures of the glutamate and serine complexes and a closed apo state

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