(2S,3S,4S) α-(Carboxycyclopropyl) glycine is a novel agonist of metabotropic glutamate receptors

Nakagawa, Yuzo; Saitoh, Kyoshi; Ishihara, Takafumi; Ishida, Michiko; Shinozaki, Haruhiko

doi:10.1016/0014-2999(90)90686-z

Cited by 77 publications

(35 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(IS,3R)-ACPD and L-CCG-I, which have been established as potent agonists for metabotropic glutamate receptors (Nakagawa et al, 1990;Ishida et al, 1990b;Hayashi et al, 1992;Krogsgaard-Larsen & Hansen, 1992;Schoepp et al, 1992), possess a glutamate skeleton in their molecules which takes an extended form. Although the active form of other agonists for metabotropic glutamate receptors is not always known, it seems reasonable to assume that one of the possible conformations for activating metabotropic glutamate receptors is an extended form (Ishida et al, 1990b).…”

Section: Discussionmentioning

confidence: 99%

“…The depolarizing responses to L-CCG-I and (IS,3R)-ACPD were neither depressed by selective NMDA antagonists nor by a non-NMDA blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), demonstrating a clear preference for non-NMDA, non-kainate and non-AMPA receptors (Shinozaki et al, 1989b). L-CCG-I stimulates phosphoinositide hydrolysis in a concentrationdependent manner in rat hippocampal synaptoneurosomes (Nakagawa et al, 1990), and it induces chloride-mediated oscillatory responses in Xenopus oocytes injected with rat brain mRNA in a manner quite similar to quisqualate or trans-ACPD (Ishida et al, 1990b). Thus, L-CCG-I proved to be a potent agonist for metabotropic glutamate receptors.…”

Section: Introductionmentioning

confidence: 99%

“…This glutamate receptor subtype in the mammalian central nervous system is activated by some kinds of glutamate analogues such as quisqualate, ibotenate, I-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the (2S,l'S,2'S)-isomer (L-CCG-I, previously reported as (2S,3S,-4S)-CCG) of 2-(carboxycyclopropyl)glycine (CCG) Sugiyama et al, 1989;Schoepp et al, 1990;Nakagawa et al, 1990;Ishida et al, 1990b;Porter et al, 1992). (1S,3R)-ACPD and L-CCG-I appeared to be selective agonists for this receptor (Irving et al, 1990;Shinozaki et al, 1989b;Ishida et al, 1990b) and others are non-selective agonists.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord

Ishida

Saitoh

Shimamoto

et al. 1993

British J Pharmacology

189

View full text Add to dashboard Cite

Neuropharmacological actions of a novel metabotropic glutamate receptor agonist, (2S,1′R,2′R,3′R)‐2‐(2,3‐dicarboxycyclopropyl)glycine (DCG‐IV), were examined in the isolated spinal cord of the newborn rat, and compared with those of the established agonists of (2S,1′S,2′S)‐2‐(carboxycyclopropyl)glycine (l‐CCG‐I) or (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid ((1S,3R)‐ACPD). At concentrations higher than 10 μm, DCG‐IV caused a depolarization which was completely blocked by selective N‐methyl‐d‐aspartate (NMDA) antagonists. The depolarization was pharmacologically quite different from that caused by l‐CCG‐I and (1S,3R)‐ACPD. DCG‐IV reduced the monosynaptic excitation of motoneurones rather than polysynaptic discharges in the nanomolar range without causing postsynaptic depolarization of motoneurones. DCG‐IV was more effective than l‐CCG‐I, (1S,3R)‐ACPD or l‐2‐amino‐4‐phosphonobutanoic acid (l‐AP4) in reducing the monosynaptic excitation of motoneurones. DCG‐IV (30 nm–1 μm) did not depress the depolarization induced by known excitatory amino acids in the newborn rat motoneurones, but depressed the baseline fluctuation of the potential derived from ventral roots. Therefore, DCG‐IV seems to reduce preferentially transmitter release from primary afferent nerve terminals. Depression of monosynaptic excitation caused by DCG‐IV was not affected by any known pharmacological agents, including 2‐amino‐3‐phosphonopropanoic acid (AP3), diazepam, 2‐hydroxysaclofen, picrotoxin and strychnine. DCG‐IV has the potential of providing further useful information on the physiological function of metabotropic glutamate receptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord

Ishida

Saitoh

Shimamoto

et al. 1993

British J Pharmacology

189

View full text Add to dashboard Cite

show abstract

“…1) [99][100][101]. LY354740 was described in 1997 as the first potent and selective agonist for mGlu2/3.…”

Section: Mglu2/3 Receptor Agonist/mglur2 Receptor Potentiatorsmentioning

confidence: 99%

Metabotropic Glutamate Receptors: Potential Drug Targets for Psychiatric Disorders

Yasuhara¹

2010

TOMCJ

View full text Add to dashboard Cite

Metabotropic glutamate receptors (mGlu receptors) have emerged as new therapeutic targets for psychiatric disorders, such as schizophrenia, depression and anxiety with their regulatory roles in glutamatergic transmissions. To date, several ligands selective for each mGlu receptor have been synthesized, and pharmacological significances of these ligands have been demonstrated in animal models. Among them, mGlu2/3 receptor agonists have been proven to be effective for treating schizophrenia and anxiety disorders in clinical studies, which may prove utilities of mGlu receptor ligands for the treatment of psychiatric disorders. This article reviews recent advances in development of each mGlu receptor ligands and their therapeutic potential.

show abstract

“…Class II and III mGluRs (mGluR2, mGluR3, mGluR4, mGluR6, mGluR7, and mGluRS) are negatively coupled to adenylyl cyclase Schoepp and Conn 1993). Some kinds of glutamate analogs, namely quisqualate, ibotenate, 1-aminocyclopentane-l,3-dicarboxic acid (ACPD), (2S, 1 + S, 2 + S)-carboxycyclopropyl glycine (L-CCG I), and (2S, 1 + R, 2 + R, 3 + R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), appear to be selective agonists for mGluRs in the mammalian central nervous system (Monaghan et al 1989;Sugiyama et al 1989;Ishida et al 1990Ishida et al 1993aNakagawa et al 1990;Schoepp et al 1990;Porter et al 1992;Shinozaki and Ishida 1992). Specific antagonists, however, have been lacking.…”

Section: Introductionmentioning

confidence: 99%

Metabotropic glutamate receptors in spatial and nonspatial learning in rats studied by means of agonist and antagonist application.

Riedel¹,

Wetzel²,

Reymann³

1995

Learn. Mem.

View full text Add to dashboard Cite

We examined the effects of both the metabotropic glutamate receptor (mGluR) antagonist MCPG and the agonist tADA in two behavioral paradigms in rats: (1) brightness discrimination and (2) spatial alternation. Compounds were applied intracerebroventricularly at different times, either 30 min prior to training or immediately after training, and rats were tested for retention 24 hr later in the same paradigms. Both MCPG and tADA caused amnesia in the spatial alternation test, when applied pretraining, but no effect was obtained in the brightness discrimination paradigm. Drug-induced amnesia was shown not to be attributable to state-dependent effects of MCPG or tADA. Moreover, the memory inhibiting effect of MCPG was dose dependent, with a low dose (20 raM/5 ml) having no effect on learning and memory and a 10 times higher concentration (200 mM/5 ml) causing complete amnesia. Application of both saline and MCPG immediately post-training prevented memory formation, which may be attributable to an interference by the injection procedure with the process of memory formation. The mGluR agonist tADA, however, facilitated memory formation in the spatial alternation task, when injected immediately after training. 3Corresponding author. Present address:

show abstract

(2S,3S,4S) α-(Carboxycyclopropyl) glycine is a novel agonist of metabotropic glutamate receptors

Cited by 77 publications

References 4 publications

A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord

A novel metabotropic glutamate receptor agonist: marked depression of monosynaptic excitation in the newborn rat isolated spinal cord

Metabotropic Glutamate Receptors: Potential Drug Targets for Psychiatric Disorders

Metabotropic glutamate receptors in spatial and nonspatial learning in rats studied by means of agonist and antagonist application.

Contact Info

Product

Resources

About