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Query: CAS:22059-21-8 (1-aminocyclopropanecarboxylic acid)
 162 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the roles of glycine in neurotoxicity caused by NMDA, primary rat cortical cultures were exposed to 100-300 microM NMDA plus glycine (0-3000 microM) or other glycine analogs in a simple saline solution, and toxicity was assessed by the amount of lactate dehydrogenase (LDH) released from the cultures. NMDA-induced neurotoxicity was abolished by 100 microM D-2-amino-5-phosphonovaleric acid (D-APV), phencyclidine (IC50, 4.1 microM), and Mg (IC50, 7.5 mM), or by reducing [Ca]0 to 0.1 mM. NMDA-induced neurotoxicity could also be abolished by 7-chlorokynurenic acid (IC50, 8.6 microM), suggesting the presence of residual glycine in the culture medium (confirmed by high-performance liquid chromatography measurement). Moreover, in the presence of 30 microM 7-chlorokynurenic acid, glycine, D-serine, D-alanine, beta-fluoro-D-alanine, and 1-aminocyclopropanecarboxylic acid could restore the neurotoxic action of NMDA, and their relative potencies and relative efficacies were the same as measured in electrophysiological assays in Xenopus oocytes or cultured neurons. The addition of greater than 100 microM glycine doubled the excitotoxic effect of NMDA. The potency of glycine was low (EC50, 27 microM), and this effect was not due to a direct action on the NMDA receptor. The above-mentioned agonists were unable to substitute for glycine, even at high concentrations (1 mM). On the other hand, beta-alanine, taurine, and GABA (1 mM) did potentiate NMDA neurotoxicity, and strychnine (IC50, 550 nM) could greatly reduce neurotoxicity in the presence of 1 mM glycine plus 300 microM NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dual effect of glycine on NMDA-induced neurotoxicity in rat cortical cultures. 198 Jan 34

In Xenopus oocytes, injected with mRNA from the brain of the rat, the characteristics of the cyclic homologues of glycine, ACPC, ACBC and cycloleucine have been examined. 1-Aminocyclopropane-1-carboxylate was a potent agonist at the NMDA-associated glycine site (EC50 = 0.09 +/- 0.02 microM) and exhibited characteristics consistent with a partial agonist. 1-Aminocyclobutane-1-carboxylate, in addition to its previously described antagonist properties, was found to possess agonist properties of low efficacy. Furthermore, ACBC did not completely block NMDA/glycine-induced currents, which is also consistent with partial agonist characteristics. In addition, small concentrations of glycine (less than 3 microM) did not alter the potency of ACBC, possibly suggesting that it is not simply a competitive glycine antagonist. Cycloleucine was a very weak glycine antagonist. These results suggest that as the size of the ring of cyclic homologues of glycine increases, there is a resulting transition from agonist to mixed agonist/antagonist to antagonist properties.
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PMID:Pharmacological characteristics of cyclic homologues of glycine at the N-methyl-D-aspartate receptor-associated glycine site. 217 61

1-Aminocyclopropanecarboxylic acid is a high affinity ligand with partial agonist properties at strychnine-insensitive glycine sites associated with the N-methyl-D-aspartate subtype of glutamate receptors. Since occupation of these sites appears required for operation of N-methyl-D-aspartate, receptor coupled cation channels, it was hypothesized that a glycine partial agonist could function as an N-methyl-D-aspartate antagonist. This hypothesis was examined by evaluating the in vivo and in vitro neuroprotective actions of 1-aminocyclopropanecarboxylic acid. 1-Aminocyclopropanecarboxlic acid (150-600 mg kg-1) administered to gerbils five minutes following twenty minutes of forebrain ischemia significantly improved seven day survival; the optimal dose (300 mg kg-1) increased 7 days survival > 4-fold, from 20% to 92%. Survival of hippocampal CA1 neurons (quantitated 7 days post-ischemia) was significantly (approximately 3-fold) increased by the 600 mg kg-1 dose. Seven day survival was not significantly increased when the interval between reperfusion and drug administration (300 mg kg-1) was increased from 5 to 30 min. In cerebellar granule cell cultures, NMDA combined with a saturating concentration of glycine (10 microM) resulted in a 500% increase in cGMP levels. cGMP levels were increased by 100% over basal when NMDA was combined with a saturating (10 microM) concentration of ACPC, indicating that in this measure, the efficacy of ACPC relative to glycine was approximately 0.2. Consistent with previous findings, 1-aminocyclopropanecarboxylic acid significantly reduced glutamate-induced neurotoxicity in cerebellar granule cell cultures. ACPC was most effective in blocking neurotoxicity at glutamate concentrations producing low to moderate levels of cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neuroprotective actions of 1-aminocyclopropanecarboxylic acid (ACPC): a partial agonist at strychnine-insensitive glycine sites. 747 40

Chronic dosing with the glycine partial NMDA agonist, 1-aminocyclopropanecarboxylic acid (ACPC) elicited an altered allosteric regulation of cortical NMDA receptor binding. The present study hypothesized that these allosteric receptor binding changes would be manifest as pharmacologically functional reductions in NMDA receptor activity following chronic ACPC dosing. NMDA inhibition of carbachol-induced phosphoinositide (PI) hydrolysis was used as a functional assay to assess NMDA receptor function in rat cerebral cortex. NMDA inhibition of stimulated PI turnover was similar in naive (46% +/- 4.5%; mean +/- SE; n = 34) and ACPC dosed rats (39% +/- 2.3%; n = 34). While ACPC reversed NMDA's inhibitory effects in naive rats (80% +/- 13%; n = 9), it was ineffective (P < 0.05) in ACPC pretreated rats (48% +/- 9.8%; n = 9). In contrast, the NMDA antagonists, MK-801 (ion channel), 7-chlorokynurenic acid (glycine site) and AP-7 (glutamate site), effectively reversed NMDA's inhibitory effects in naive and ACPC treated rats. The potency of these antagonists were unaltered by prior ACPC dosing. Thus, chronic ACPC therapy does not alter the functioning of the NMDA ion channel or glutamate receptor sites, but elicits functional tolerance to ACPC's actions in the cortical NMDA complex.
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PMID:Chronic dosing with 1-aminocyclopropanecarboxylic acid, a glycine partial agonist, modulates NMDA inhibition of muscarinic-coupled PI hydrolysis in rat cortical slices. 971 86

The present studies assessed the effects of both systemic and intraaccumbens injections of 1-aminocyclopropanecarboxylic acid (ACPC), and NMDA partial agonist, on ethanol consumption in a limited access procedure in Wistar rats. Systemically administered ACPC reduced ethanol consumption in a dose-dependent manner, while a single dose of ACPC administered bilaterally into the nucleus accumbens also reversibly reduced ethanol consumption. Indirect measures of general appetitive behavior showed no effect of ACPC on weight or water intake, which suggests that this effect of ACPC may be specific to ethanol. These data are compatible with the role of NMDA receptors in modulating ethanol consumption and provide the first data showing that ACPC can reduce ethanol consumption. ACPC has neuroprotective effects and does not show the psychotomimetic effects observed with NMDA receptor agents. Thus, ACPC may be helpful in future clinical studies designed to reduce alcohol use.
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PMID:The NMDA receptor partial agonist, 1-aminocyclopropanecarboxylic acid (ACPC), reduces ethanol consumption in the rat. 1054 75

Recently, we have shown that 1-aminocyclopropanecarboxylic acid (ACPC) acts simultaneously as a high affinity full glycine agonist and a low affinity glutamate site competitive antagonist for NMDA receptor channels. In this paper, we have attempted to determine the subunit specificity and mechanism of action of a different putative cyclic partial agonist, D-cycloserine (DCS). NMDA receptor currents were measured utilizing the two-electrode voltage clamp technique on Xenopus oocytes injected with NR1-1a cRNA and either NR2A, NR2B or NR2C cRNA. Efficacies of DCS were 35-68% of glycine controls for channels containing NR1-1a and NR2A or NR2B subunits, but channels containing NR2C subunits had efficacies greater than glycine controls (192%). Unlike ACPC, DCS efficacy does not increase with increasing NMDA concentration; however, the lowered efficacy elicited by DCS results solely through its interaction with the glycine binding site. The efficacy of DCS was pH sensitive for NR2A or NR2B-containing channels, but not for channels containing NR2C. From this, we suggest that the protonated and deprotonated forms of DCS when bound, probably open NMDA channels with different efficiency. Two models compatible with these results are presented.
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PMID:Subunit specificity and mechanism of action of NMDA partial agonist D-cycloserine. 1148 51

ACPC (1-aminocyclopropanecarboxylic acid) is a partial agonist at the strychnine-insensitive glycine receptor site on the NMDA receptor complex, and a functional NMDA antagonist. A series of experiments was conducted to assess the effects of ACPC in a biased place conditioning paradigm. As previously reported, ACPC itself did not support either appetitive or aversive place conditioning. However, co-administration of ACPC (200 mg/kg) blocked the acquisition of place preferences conditioned using a variety of psychoactive drugs (amphetamine, cocaine, nomifensine, diazepam, morphine, nicotine). No tolerance was seen to this effect following two weeks of chronic ACPC administration. Overall, ACPC did not affect the expression of place conditioning when administered immediately before the post-conditioning test. However, these effects appeared somewhat variable between drugs, and further analysis showed that ACPC did block the expression of preferences conditioned with some drugs (diazepam, morphine, nicotine), but not others (amphetamine, cocaine, nomifensine). The effects of ACPC could not be accounted for by state dependence, as ACPC blocked morphine and cocaine place preferences when administered during both the acquisition and the expression phase of conditioning. In contrast to the blockade by ACPC of drug-induced place preferences, ACPC had no effect on the acquisition of place preferences conditioned using a variety of natural non-drug reinforcers (food, sucrose, social interaction, novelty). ACPC also had no effect on the acquisition of drug-induced place aversions (naloxone, picrotoxin). Thus, ACPC selectively blocked appetitive conditioning by drug reinforcers, without affecting either appetitive conditioning by natural reinforcers or drug-induced aversions. As place preference conditioning has been demonstrated to have high predictive validity for detecting compounds with an abuse potential in humans, this selective action suggests that ACPC might have some clinical utility in the treatment of addiction, without affecting responses to natural rewards.
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PMID:Selective blockade of drug-induced place preference conditioning by ACPC, a functional NDMA-receptor antagonist. 1243 48

The status epilepticus (SE) induced in rats by lithium-pilocarpine (Li-pilo) shares many common features with soman-induced SE including a glutamatergic phase that is inhibited by NMDA antagonists. The present study determined whether 1-aminocyclopropanecarboxylic acid (ACPC) or D-cycloserine (DCS), both partial agonists of the strychnine-insensitive glycine site on the NMDA receptor ionophore complex, exerted anticonvulsant or neuroprotectant activity in Li-pilo SE. ACPC or DCS were administered either immediately following pilocarpine (exposure treatment) or 5 min after the onset of SE as determined by ECoG activity. SE was allowed to proceed for 3 h before termination with propofol. The rats were sacrificed 24 h following pilocarpine administration. Neither drug had an effect on the latency to seizure onset or the duration of seizure activity. ACPC administered 5 min after SE onset produced significant neuroprotection in cortical regions, amygdala and CA1 of the hippocampus. In contrast, when administered as exposure treatment ACPC enhanced the neural damage in the thalamus and CA3 of the hippocampus suggesting the neuropathology in those regions is mediated by a different subset of NMDA receptors. DCS had no neuroprotectant activity in Li-pilo SE but exacerbated neuronal damage in the thalamus. Neither drug affected the cholinergic convulsions but both had differential effects on neural damage. This suggests that the SE-induced seizure activity and subsequent neuronal damage involve independent mechanisms.
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PMID:Differential neuroprotective effects of the NMDA receptor-associated glycine site partial agonists 1-aminocyclopropanecarboxylic acid (ACPC) and D-cycloserine in lithium-pilocarpine status epilepticus. 1528 14