Abstract
A new metabotropic glutamate receptor (mGluR) agonist, (2 S,1′ S,2′ S)-2-(2-carboxy-3,3-difluorocyclopropyl)glycine (L-F 2CCG-I), induces a priming effect on ( RS)-α-aminopimelate in the isolated spinal cord of newborn rats. Similar to ( RS)-α-aminopimelate, l-glutamate (30–100 μM) neither affected spinal reflexes nor the resting membrane potentials of motoneurones, but preferentially potentiated the depression of monosynaptic excitation caused by L-F 2CCG-I (0.4 μM). Following L-F 2CCG-I treatment (1–2 μM), l-glutamate decreased the monosynaptic spinal reflexes in a concentration dependent manner, indicating a ‘priming’ effect of L-F 2CCG-I. Thus l-glutamate is completely compatible with ( RS)-α-aminopimelate in revealing the priming effect. An anion transport blocker, 4,4′-dinitrostilbene-2,2′-disulphonic acid (DNDS) (100 μM), markedly inhibited both the response to ( RS)-α-aminopimelate and the induction of the L-F 2CCG-I priming effect. The data suggest that L-F 2CCG-I is Cl −-dependently incorporated into certain stores, and that ( RS)-α-aminopimelate or l-glutamate must stimulate the release of L-F 2CCG-I from the storage site. There were pharmacological similarities between the quisqualate and L-F 2CCG-I priming effect. The physiological significance of the quisqualate or L-F 2CCG-I priming is not yet established. L-F 2CCG-I would be expected to be a useful pharmacological probe for elucidating the mechanism of the priming.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call