Antibiotics versus no treatment for asymptomatic bacteriuria in residents of aged care facilities: a systematic review and meta-analysis

l-Glutamate (Glu) activates at least eight different G protein-coupled receptors known as metabotropic glutamate (mGlu) receptors, which mostly act regulators of synaptic transmission. These consist two domains: an extracellular domain in agonists bind and a transmembrane heptahelix region involved protein activation. Although new mGlu receptor antagonists have been described, few are selective for single subtype. Here, we examined the effects novel compound, BAY36-7620 [(3aS,6aS)- 6a-Naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on], on (mGlu1–8), transiently expressed human embryonic kidney 293 cells. is potent (IC50 = 0.16 μM) antagonist mGlu1 inhibits >60% mGlu1a constitutive activity (IC50 0.38 μM). therefore first described inverse agonist. To address mechanism action BAY36-7620, Glu dose-response curves were performed presence increasing concentrations BAY36-7620. The results show that largely decreases maximal effect Glu. Moreover, did not displace [3H]quisqualate binding from Glu-binding pocket, further indicating noncompetitive antagonist. Studies chimeric containing regions DmGluA, mGlu2, or mGlu5, revealed necessary Transmembrane helices 4 to 7 shown play critical role selectivity This specific site differs competitive indicates plays pivotal agonist-independent this receptor. will be useful delineate functional importance receptor, including its putative activity.