Metabotropic glutamate receptor subtypes mediating slow inward tail current (IADP) induction and inhibition of synaptic transmission in olfactory cortical neurones
Authors: Libri Vincenzo , Constanti Andrew , Zibetti Maurizio , Postlethwaite Michael 
Published: August 2006

The pharmacological features of the pre‐ and postsynaptic metabotropic glutamate receptors (mGluRs) present in the guinea‐pig olfactory cortex, were examined in brain slices in vitro by use of a conventional intracellular current clamp/voltage clamp recording technique.

Bath‐application of trans‐aminocyclopentane‐1,3‐dicarboxylic acid (trans‐ACPD) (50 μm) produced a sustained membrane depolarization, increase in cell excitability and induction of a post‐stimulus inward (afterdepolarizing) tail current (IADP) (measured under ‘hybrid’ voltage clamp) similar to those evoked by the muscarinic receptor agonist oxotremorine‐M (OXO‐M, 2 μm).

l‐Glutamate (0.25–1 mm, in the presence of 20 μm 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) and 100 μm dl‐amino‐5‐phosphono valeric acid (dl‐APV)) or the broad spectrum mGluR agonists 1S,3R‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD, 10 μm), 1S,3S‐ACPD (50 μm), ibotenate (Ibo; 25 μm, in the presence of 100 μm dl‐APV), the selective mGluR I agonists (S)‐3,5‐dihydroxyphenylglycine ((S)‐3,5‐DHPG, 10 μm), (S)‐3‐hydroxyphenylglycine ((S)‐3HPG, 50 μm), or quisqualate (10 μm, in the presence of 20 μm CNQX), but not the mGluR II agonist 2S,1′S,2′S‐2‐(2′‐carboxycyclopropyl)‐glycine (l‐CCGI, 1 μm) or mGluR III agonist l(+)‐2‐amino‐4‐phosphonobutyric acid (l‐AP4, 1 mm), were all effective in producing membrane depolarization and inducing a post‐stimulus IADP. Unexpectedly, the proposed mGluR II‐selective agonist (2S,1′R,2′R,3′R)‐2‐(2′,3′‐dicarboxycyclopropyl)‐glycine (DCG‐IV, 10 μm, in the presence of 100 μm dl‐APV) was also active.

The excitatory effects induced by 10 μm 1S,3R‐ACPD were reversibly antagonized by the mGluR I/II antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine ((+)‐MCPG, 0.5–1 mm), as well as the selective mGluR I antagonists (S)‐4‐carboxyphenylglycine ((S)‐4CPG) and (S)‐4‐carboxy‐3‐hydroxyphenyl glycine ((S)‐4C3HPG) (both at 1 mm), but not the nonselective mGluR antagonist l(+)‐2‐amino‐3‐phosphonopropionic acid (l‐AP3, 1 mm) or the selective mGluR III antagonist (S)‐α‐methyl‐l‐AP4 (MAP4, 1 mm).

The excitatory postsynaptic potentials (e.p.s.ps), induced by single focal stimulation of cortical excitatory fibre tracts, were markedly reduced by 1S,3R‐ACPD or l‐AP4 (both at 10 μm), and by the selective mGluR II agonists (mGluR I antagonists) (S)‐4CPG or (S)‐4C3HPG (both at 1 mm) but not (S)‐3,5‐DHPG or (S)‐3HPG (both at 100 μm).

The inhibitory effects of 1S‐3R‐ACPD, but not l‐AP4, were reversibly blocked by (+)‐MCPG (1 mm), whereas those produced by l‐AP4, but not 1S,3R‐ACPD, were blocked by the selective mGluR III antagonist MAP4 (1 mm).

It is concluded that a group I mGluR is most likely involved in mediating excitatory postsynaptic effects, whereas two distinct mGluRs (e.g. group II and III) might serve as presynaptic inhibitory autoreceptors in the guinea‐pig olfactory cortex.

British Journal of Pharmacology (1997) 120, 1083–1095; doi:10.1038/sj.bjp.0701021