NMDA (N-methyl-D-aspartate) receptor

The glutamate-induced increase in Arc/Arg3.1 protein levels is partially inhibited by DL-AP5 (100 μM) [5]. Arc/Arg3.1's NMDA-induced upregulation is reduced by DL-AP5 [5].

DL-AP5 (0-10 μg/rat, Intra-CA1) greatly diminishes the effect of NMDA [3]. DL-AP5 (0-10 nmol, intracerebroventricular injection) promotes a dose-dependent increase in food consumption [4]. DL-AP5 (5 nmol, intracerebroventricular injection) attenuates the reduction in food consumption generated by intracerebroventricular injection of ghrelin [4].

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This study was designed to examine the effects of intracerebroventricular injection of DL-AP5 (N-methyl-D-aspartate (NMDA) receptor antagonist) and glutamate on ghrelin-induced feeding behavior in 3-h food-deprived (FD3) broiler cockerels. At first, guide cannula was surgically implanted in the right lateral ventricle of chickens. In experiment 1, birds were intracerebroventricularly injected with 0, 2.5, 5, and 10 nmol of DL-AP5. In experiment 2, chickens received 5 nmol DL-AP5 prior to the injection of 0.6 nmol ghrelin. In experiment 3, birds were administered with 0.6 nmol ghrelin after 300 nmol glutamate, and the cumulative feed intake was determined at 3-h postinjection. The results of this study showed that the intracerebroventricular injection of DL-AP5 increased food consumption in FD3 broiler cockerels (P ≤ 0.05), and this increase occurs in a dose-dependent manner. Moreover, the decreased food intake induced with the intracerebroventricular injection of ghrelin was additively enhanced by pretreatment with glutamate, and this effect was attenuated by DL-AP5 administration(P ≤ 0.05).These results suggest that there is an interaction between ghrelin and glutamatergic system (through NMDA receptor) on food intake in broiler cockerels.[4]

Animal/Disease Models: Male Wistar rat (180-230 g) [3]
Doses: 1, 3.2 and 10 μg/rat
Route of Administration: Inject into the dorsal hippocampus (within CA1) immediately after electric shock, one time
Experimental Results:Significant reduction There was a significant interaction effect of NMDA (10-2 μg/rat, within CA1).

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Animal/Disease Models: Broiler chicken (FD3) (3 hrs (hrs (hours)) fast, n=8 per group) [4]
Doses: 0, 2.5, 5 and 10 nmol; volume of 10 µL
Route of Administration: intracerebroventricular injection
Experimental Results: dose causing food consumption The dependence increased, being significant for the 5 and 10 nmol doses.

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Animal/Disease Models: broiler rooster (fasted for 3 hrs (hrs (hours)) (FD3), n=8 per group) [4]
Doses: 5 nmol
Route of Administration: intracerebroventricular injection, followed by ghrelin (0.6 nmol)
Experimental Results: Attenuated by Intracerebroventricular injection of ghrelin.

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To determine the involvement of glutamate NMDA receptor in the brain in ghrelin-induced eating response, effects of centrally administered DL-AP5 and glutamate on ghrelin-induced eating response were determined in chickens. Injections were made with a 29-gauge, thin-walled stainless-steel injection cannula which extends 1.0 mm beyond the guide cannula. This injection cannula was connected to a 10-μl Hamilton syringe connected to a 60 cm length of PE-20 tubing. Solutions were injected over a period of 60 s. Another 60-s period was allowed to permit the solution to diffuse from the tip of the cannula into the ventricle. All experimental procedures were performed between 9 a.m. and 2 p.m. Before the injections, the birds were removed from their individual cages, restricted by hand, and after injections were put back into their cages. Birds were handled and mock-injected daily during the 5 days recovery period to habituate them to the injection procedure. Three hours before the beginning of the experiments, animals were deprived of food but with water ad lib. Immediately after injections, the birds were returned to their cages. Fresh food was supplied at the time of injection, and cumulative feed intake (grams) was recorded at 15, 30, 60, 120, and 180 min after injection. Placement of the guide cannula into the ventricle was verified by the presence of cerebrospinal fluid and intracerebroventricular injection of methylene blue and anatomically slicing the frozen brain tissue at the end of the experiments.[4]
Experiment 1 was designed to examine the effect of intracerebroventricular injections of different DL-AP5 doses on cumulative feed intake in 3-h food-deprived (FD3, n = 8 for each group) chickens. For this purpose, the birds received 0, 2.5, 5, and 10 nmol of DL-AP5 in a volume of 10 μl. Control group was injected with 10 μl of 0.9% NaCl solution.[4]
In experiment 2, birds of each group received two injections. The first injection consisted of either 0 or 5 nmol DL-AP5 in a volume of 5 μl. The second injection consisted of either 0 or 0.6 nmol ghrelin in a volume of 5 μl, 15 min after the first injection as described in Table 1 (n = 7–9 for each group).[4]

[1]. Neurokinin and NMDA antagonists (but not a kainic acid antagonist) are antinociceptive in the mouse formalin model. Pain. 1991;44(2):179-185.

[2]. N-methyl-D-aspartate receptors of ganglion cells in rabbit retina. J Neurophysiol. 1990;63(1):16-30.

[3]. Jafari-Sabet M. NMDA receptor blockers prevents the facilitatory effects of post-training intra-dorsal hippocampal NMDA and physostigmine on memory retention of passive avoidance learning in rats. Behav Brain Res. 2006 Apr 25;169(1):120-7.

[4]. The effects of DL-AP5 and glutamate on ghrelin-induced feeding behavior in 3-h food-deprived broiler cockerels. J Physiol Biochem. 2011 Jun;67(2):217-23.

[5]. Glutamate-induced rapid induction of Arc/Arg3.1 requires NMDA receptor-mediated phosphorylation of ERK and CREB. Neurosci Lett. 2017 Nov 20;661:23-28.

2-amino-5-phosphonopentanoic acid is the 5-phosphono derivative of 2-aminopentanoic acid; acts as an N-methyl-D-aspartate receptor antagonist. It has a role as a NMDA receptor antagonist. It is functionally related to a phosphonic acid and a 2-aminopentanoic acid.
2-Azaniumyl-5-phosphonopentanoate has been reported in Euglena gracilis with data available.

C5H12NO5P

197.1262

197.045

C, 30.47; H, 6.14; N, 7.11; O, 40.58; P, 15.71

76326-31-3

D-AP5;79055-68-8;L-AP5;79055-67-7

1216

White to off-white solid powder

1.5±0.1 g/cm3

482.1±55.0 °C at 760 mmHg

245.4±31.5 °C

0.0±2.6 mmHg at 25°C

1.536

-2.32

4

6

5

12

200

0

VOROEQBFPPIACJ-UHFFFAOYSA-N

InChI=1S/C5H12NO5P/c6-4(5(7)8)2-1-3-12(9,10)11/h4H,1-3,6H2,(H,7,8)(H2,9,10,11)

2-amino-5-phosphonopentanoic acid

76326-31-3; DL-AP5; 2-Amino-5-phosphonopentanoic acid; DL-2-Amino-5-phosphonopentanoic acid; 5-Phosphononorvaline; 2-AMINO-5-PHOSPHONOVALERATE; 2-Amino-5-phosphovaleric acid; 2-Amino-5-phosphonovaleric Acid;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~33.33 mg/mL (~169.08 mM)

Solubility in Formulation 1: 50 mg/mL (253.64 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)