Group I, II, and III mGluR Compounds Affect Rhythm Generation in the Gastric Circuit of the Crustacean Stomatogastric Ganglion

Abstract

We have studied the effects of group I, II, and III metabotropic glutamate receptor (mGluR) agonists on rhythm generation by the gastric circuit of the stomatogastric ganglion (STG) of the Caribbean spiny lobster Panulirus argus. All mGluR agonists and some antagonists we tested in this study had clear and distinct effects on gastric rhythm generation when superfused over combined oscillating or blocked silent STG preparations. A consistent difference between group I agonists and group II and III agonists was that group I agonists acted excitatory. The group I-specific agonists l-quisqualic acid and ( S)-3,5-dihydroxyphenylglycine, as well as the nonspecific agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid accelerated ongoing rhythms and could induce gastric rhythms in silent preparations. The group II agonist (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (L-CCG-I) and the group III agonist l(+)-2-amino-4-phosphonobutyric acid (l-AP4) slowed down or completely blocked ongoing gastric rhythms and were without detectable effect on silent preparations. The action of L-CCG-I was blocked partially by the group-II-specific antagonist, (RS)-1-amino-5-phosphonoindan-1-carboxylic acid [(RS)APICA], and the group-III-specific antagonist (RS)-α-methyl-4-phosphonophenylglycine completely blocked the action of l-AP4. Besides its antagonistic action, the group-II-specific antagonist (RS)APICA had a remarkably strong apparent inverse agonist action when applied alone on oscillating preparations. The action of all drugs was dose dependent and reversible, although recovery was not always complete. In our experiments, the effects of none of the mGluR-specific agonists were antagonized or amplified by the N-methyl-d-aspartate (NMDA)-receptor-specific antagonistd(−)-2-amino-5-phosphonopentanoic acid, excluding the contamination of responses to mGluR agonists by nonspecific cross-reactivity with NMDA receptors. Picrotoxin did not prevent the inhibitory action of L-CCG-I and l-AP4. We conclude that mGluRs, probably similar to those belonging to groups I, II, and III described in mammals, may play a role as modulators of gastric circuit rhythm generation in vivo.