ACTIONS OF PHENYLGLYCINE ANALOGS AT SUBTYPES OF THE METABOTROPIC GLUTAMATE-RECEPTOR FAMILY

被引：144

作者：

THOMSEN, C ^{[1
]}

BOEL, E ^{[1
]}

SUZDAK, PD ^{[1
]}

机构：

[1] NOVO NORDISK A-S,DEPT MOLEC BIOL,DK-2760 MALOV,DENMARK

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1994年 / 267卷 / 01期

关键词：

METABOTROPIC GLUTAMATE RECEPTOR; PHENYLGLYCINE DERIVATIVE; (1S,3R)-ACPD (1S,3R)-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLATE; PHOSPHOINOSITIDE HYDROLYSIS; CYCLIC AMP;

D O I：

10.1016/0922-4106(94)90227-5

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The functional effects of phenylglycine analogs on metabotropic glutamate receptor (mGluR) subtypes mGluR1alpha, mGluR2 and mGluR4 were examined. (S)-4-Carboxyphenylglycine (IC50 = 65 +/- 5 muM), (PS)-alpha-methyl-4-carboxyphenylglycine (IC50 = 155 +/- 38 muM) and (S)-3-carboxy-4-hydroxyphenylglycine (IC50 = 290 +/- 47 AM) competitively antagonized glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidney (BHK) cells stably expressing mGluRa1alpha. (S)-4-Carboxyphenylglycine and (R,S)-alpha-methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing mGluR2 With IC50 values of 577 +/- 74 muM and 340 +/- 59 muM, respectively. (PS)-4-carboxy-3-hydroxyphenylglycine, (R)-3-hydroxyphenylglycine and (S)-3-carboxy-4-hydroxyphenylglycine were agonists at mGluR2 with EC50 values of 48 +/- 5 muM, 451 +/- 93 and 97 +/- 12 muM, respectively. In parallel experiments, no activities of these phenylglycine analogs at mGluR4 were observed. The present report demonstrates that phenylglycine analogs possess differential functional activities at subtypes of the mGluR family.

引用

页码：77 / 84

页数：8

共 26 条

[1]

ABE T, 1992, J BIOL CHEM, V267, P13361

[2] SIGNAL TRANSDUCTION AND PHARMACOLOGICAL CHARACTERISTICS OF A METABOTROPIC GLUTAMATE RECEPTOR, MGLUR1, IN TRANSFECTED CHO CELLS [J].

ARAMORI, I ;

NAKANISHI, S .

NEURON, 1992, 8 (04) :757-765

[3] INDUCTION OF LTP IN THE HIPPOCAMPUS NEEDS SYNAPTIC ACTIVATION OF GLUTAMATE METABOTROPIC RECEPTORS [J].

BASHIR, ZI ;

BORTOLOTTO, ZA ;

DAVIES, CH ;

BERRETTA, N ;

IRVING, AJ ;

SEAL, AJ ;

HENLEY, JM ;

JANE, DE ;

WATKINS, JC ;

COLLINGRIDGE, GL .

NATURE, 1993, 363 (6427) :347-350

[4] PHENYLGLYCINE DERIVATIVES AS NEW PHARMACOLOGICAL TOOLS FOR INVESTIGATING THE ROLE OF METABOTROPIC GLUTAMATE RECEPTORS IN THE CENTRAL-NERVOUS-SYSTEM [J].

BIRSE, EF ;

EATON, SA ;

JANE, DE ;

JONES, PLS ;

PORTER, RHP ;

POOK, PCK ;

SUNTER, DC ;

UDVARHELYI, PM ;

WHARTON, B ;

ROBERTS, PJ ;

SALT, TE ;

WATKINS, JC .

NEUROSCIENCE, 1993, 52 (03) :481-488

[5]

BIRSE EF, 1992, J PHYSIOL-LONDON, V452, pP185

[6] MEDIATION OF THALAMIC SENSORY RESPONSES INVIVO BY ACPD-ACTIVATED EXCITATORY AMINO-ACID RECEPTORS [J].

EATON, SA ;

BIRSE, EF ;

WHARTON, B ;

SUNTER, DC ;

UDVARHELYI, PM ;

WATKINS, JC ;

SALT, TE .

EUROPEAN JOURNAL OF NEUROSCIENCE, 1993, 5 (02) :186-189

[7] COMPETITIVE ANTAGONISM AT METABOTROPIC GLUTAMATE RECEPTORS BY (S)-4-CARBOXYPHENYLGLYCINE AND (RS)-ALPHA-METHYL-4-CARBOXYPHENYLGLYCINE [J].

EATON, SA ;

JANE, DE ;

JONES, PLS ;

PORTER, RHP ;

POOK, PCK ;

SUNTER, DC ;

UDVARHELYI, PM ;

ROBERTS, PJ ;

SALT, TE ;

WATKINS, JC .

EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1993, 244 (02) :195-197

[8]

FOTUHI M, 1993, J NEUROSCI, V13, P2001

[9] MICROMOLAR L-2-AMINO-4-PHOSPHONOBUTYRIC ACID SELECTIVELY INHIBITS PERFORANT PATH SYNAPSES FROM LATERAL ENTORHINAL CORTEX [J].

KOERNER, JF ;

COTMAN, CW .

BRAIN RESEARCH, 1981, 216 (01) :192-198

[10] EXPRESSION PATTERN AND PHARMACOLOGY OF THE RAT TYPE-IV METABOTROPIC GLUTAMATE-RECEPTOR [J].

KRISTENSEN, P ;

SUZDAK, PD ;

THOMSEN, C .

NEUROSCIENCE LETTERS, 1993, 155 (02) :159-162

← 1 2 3 →