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Titolo:
ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS BY L-AP4 STIMULATES SURVIVAL OF RAT CEREBELLAR GRANULE CELLS IN CULTURE
Autore:
GRAHAM ME; BURGOYNE RD;
Indirizzi:
UNIV LIVERPOOL,PHYSIOL LAB,POB 147 LIVERPOOL L69 3BX MERSEYSIDE ENGLAND
Titolo Testata:
European journal of pharmacology. Molecular pharmacology section
fascicolo: 1, volume: 288, anno: 1994,
pagine: 115 - 123
SICI:
0922-4106(1994)288:1<115:AOMGRB>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
AMINO-ACID RECEPTORS; GROWTH FACTOR-I; BRAIN-FUNCTION; G-PROTEINS; HIGH-K+; NEURONS; POTASSIUM; CALCIUM; NMDA; L-2-AMINO-4-PHOSPHONOBUTYRATE;
Keywords:
L-AP4 (L(+)-2-AMINO-4-PHOSPHONOBUTYRIC ACID); METABOTROPIC GLUTAMATE RECEPTOR; CEREBELLAR GRANULE CELL; NEUROTROPHIC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
M.E. Graham e R.D. Burgoyne, "ACTIVATION OF METABOTROPIC GLUTAMATE RECEPTORS BY L-AP4 STIMULATES SURVIVAL OF RAT CEREBELLAR GRANULE CELLS IN CULTURE", European journal of pharmacology. Molecular pharmacology section, 288(1), 1994, pp. 115-123

Abstract

The results presented here show that the metabotropic glutamate receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) is capable ofmarkedly stimulating the survival of rat cerebellar granule cells in culture. This is the first demonstration of a neurotrophic role for metabotropic glutamate receptors. The survival promoting action of L-AP4does not involve a large, rapid rise in [Ca2+](i) which is seen with other neurotrophic agents in granule cells such as N-methyl-D-aspartate, ionomycin and high potassium. In addition, the survival-promoting effect of L-AP4 did not appear to be related to changes in cAMP levels. Survival due to L-AP4 was enhanced by pertussis toxin and by forskolin and was unaffected by inhibitors of cAMP-dependent protein kinase. Measurement of cAMP levels after long-term treatment with neurotrophic agents showed no clear relationship between cAMP concentration and granule cell survival. The mechanism of L-AP4 stimulated cell survival isunknown but seems unlikely to involve an acute rise in [Ca2+](i) or modulation of cAMP levels. Survival induced by L-AP4 was not blocked bythe antagonist (RS)-alpha-methyl-4-carboxyphenylglycine. Similarity in these properties with those of the mGLu(7) receptor suggests that granule cell survival was stimulated by an mGlu(7)-like metabotropic receptor.

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Documento generato il 15/07/20 alle ore 21:30:05