Phosphoinositides metabotropic

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

Ibotenate creates neurotoxic and phosphoinositide effects through distinct receptors (Zinkand et al. 1992). The neurotoxic effects are prevented by MK-801 and enhanced by glycine, implying NMDA involvement. Phosphoinositide hydrolysis is mediated by metabotropic receptors, and is unaffected by NMDA agents. 

Facchinetti F., HackN. J., and Balazs R. (1998). Calcium influx via ionotropic glutamate receptors causes long lasting inhibition of metabotropic glutamate receptor-coupled phosphoinositide hydrolysis. Neurochem. Int. 33 263-270. 

Nicolle M. M., Colombo P. J., Gallagher M., and McKinney M. (1999). Metabotropic glutamate receptor-mediated hippocampal phosphoinositide turnover is blunted in spatial learning-impaired aged rats. J. Neurosci. 19 9604-9610. 

Hou L, Klann E. 2004. Activation of the phosphoinositide 3-kinase-akt-mammalian target of rapamycin signaling pathway is required for metabotropic glutamate receptor-dependent long-term depression. J Neurosci 24 6352-6361. 

Fotuhi M, Sharp AH, Glatt CE, Hwang PM, Von Krosigk M, Snyder SH, Dawson TM (1993) Differential localization of phosphoinositide-iinked metabotropic glutamate receptor (mGluRl) and the inositol 1,4,5-trisphosphate receptor in rat brain. J Neurosci 73 2001-2012. 

Reid SNM, Romano C, Hughes T, Daw NW (1995) Immunohistochemical study of two phosphoinositide-linked metabotropic glutamate receptors (mGluRla and mGluR5) in the cat visual cortex before, during, and after the peak of the critical period for eye-specific connections. J Comp Neurol 355 410-411. 

ACPD receptors are linked by G-proteins to the phosphoinositide-protein kinase C (PI-PKC) and adenylate cyclase-cyclic AMP second messenger systems (Conn and Desai, 1991 Winder and Conn, 1992). Actions on the PI system promote the release of Ca from intracellular stores (Conn and Desai, 1991). The most selective agonist for ACPD receptors is lS,3R-trans-ACPD, although Glu, ibotenate and Quis also act at these receptors. A related class of metabotropic receptors is activated by APB. Seven different metabotropic Glu receptors (mGluRl-7) have been cloned to date (Hollmann and Heinemann, 1994 Saugstad et al.,... 

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