Disease relevance of 3,5-Dhpg

• A 10-min application of the group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) caused a transient depression of synaptic responses but a significant enhancement of subsequent LTP for both tetanus protocols (45% and 41% LTP, respectively) [1].
• Antagonists acting on mGlu1 or mGlu5 receptors are anticonvulsant against 3,5-dihydroxyphenylglycine (DHPG)-induced seizures and in mouse models of generalized motor seizures and absence seizures [2].

High impact information on 3,5-Dhpg

• The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced contralateral rotation in a dose-dependent manner, whereas group II and group III agonists were ineffective [3].
• In vitro, the mGluR group I agonist 3,5-dihydroxyphenylglycine induced proliferation in chick spinal cord astroglial cultures [4].
• Consistent with these results, the response of Ca2+ to the selective group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), in cultured spinal cord neurons was potently enhanced by 3 days of in vitro treatment with morphine [5].
• In non-synchronized, subconfluent secondary cultures of rat cortical astrocytes, the selective group-I metabotropic glutamate (mGlu) receptor agonist 3,5-dihydroxyphenylglycine (DHPG) increased [methyl-3H]-thymidine incorporation [6].
• Bath application of a low concentration of the specific group I agonist 3,5-dihydroxyphenylglycine (DHPG), which does not affect basal synaptic transmission, resulted in a leftward shift of the frequency-response function for the induction of LTD and LTP in naïve synapses [7].

Chemical compound and disease context of 3,5-Dhpg

• (R,S)-alpha-Methyl-4-carboxyphenylglycine (200 mM/5 microliters), a metabotropic glutamate receptor antagonist, when applied prior to high-frequency tetanus and ADA or 3,5-dihydroxyphenylglycine, completely inhibited this effect [8].

Biological context of 3,5-Dhpg

• These results indicate that a distinct time window for the enhancement by ADA and 3,5-dihydroxyphenylglycine of short-term potentiation into long-term potentiation occurs in the dentate gyrus in vivo [8].
• A reduced PI hydrolysis in corticosterone-nursed rats was also observed when group-I mGlu receptors (i.e. mGlu1 and -5 receptors) were selectively activated using 3,5-dihydroxyphenylglycine or 1S,3R-APCD combined with the selective group-II mGlu receptor antagonist, 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)propionate [9].
• A selective group I mGluR agonist, 3,5-dihydroxyphenylglycine, depolarised all SPNs tested, induced oscillations in membrane potential of otherwise non-oscillating SPNs and increased the frequency of spontaneous oscillations [10].
• Co-incubation of a subthreshold dose of a group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) that itself did not alter basal pCREB expression augmented NMDA-induced CREB phosphorylation [11].
• After spontaneous arrest of bursting, rhythm was reactivated at clinically relevant or physiological concentrations by 3,5-dihydroxyphenylglycine, thyrotropin-releasing hormone, or rolipram, each affecting distinct second-messenger pathways [12].

Anatomical context of 3,5-Dhpg

• (R,S)-alpha-Methyl-4-carboxyphenylglycine blocked the effects of 3,5-dihydroxyphenylglycine, but not trans-azetidine-2,4-dicarboxylic acid in synaptosomes [13].
• An amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluR1 [14].

Associations of 3,5-Dhpg with other chemical compounds

• The mGlu receptor-dependent form of LTD can be activated by application of 3,5-dihydroxyphenylglycine (DHPG), a group I selective mGlu receptor agonist [15].
• In synaptosomes, 3,5-dihydroxyphenylglycine enhanced diacylglycerol formation and facilitated vesicular Ca(2+)-dependent glutamate release, whereas trans-azetidine-2,4-dicarboxylic acid had no effect on these processes [13].
• In wild-type animals, N-methyl-D-aspartate (NMDA)-induced membrane depolarization/inward currents were potentiated in the presence of both the group I mGluR agonist 3,5-dihydroxyphenylglycine (3,5-DHPG) and the mGluR5 selective agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) [16].
• By administering the drugs in the dialysis buffer, it was found that the group 3 mGluR agonist L-amino-4-phosphonobutyrate produced a dose-dependent reduction in extracellular dopamine, whereas the group 1 agonist 3,5-dihydroxyphenylglycine was ineffective [17].
• Preferential agonists of class I mGluRs, such as quisqualate, 3,5-dihydroxyphenylglycine (DHPG), and trans-azetidine-2,4-dicarboxylic acid (t-ADA), as well as the mixed mGluR agonist, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) all stimulated PPI hydrolysis in cultured cortical cells [18].

Gene context of 3,5-Dhpg

• Bath application of the non-selective mGluR agonist (1 S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1 S,3R-ACPD) or the group-I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) depolarized all cholinergic neurones tested by activation of an inward current at -60 mV [19].
• Application of a selective group I agonist, 3,5-dihydroxyphenylglycine (DHPG), produced much greater induction of either mRNA (285 and 289% over control for PPD and PPE after 100 microM DHPG incubation, respectively) [20].
• (S)-alpha-methyl-3-carboxyphenylalanine, which is a potent and selective antagonist for LAP4 in the cortex, is anticonvulsant in DBA/2 mice and decreases the convulsant effect of N-methyl-D-aspartate, 3,5-dihydroxyphenylglycine, LAP4 and MPPG in Swiss-Webster mice [21].

Analytical, diagnostic and therapeutic context of 3,5-Dhpg

• In urethan-anesthetized rats, unilateral 30-nl microinjections of the group I-selective mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) into the NTS decreased mean arterial pressure, heart rate, and lumbar sympathetic nerve activity [22].

References