The rat mGlu 1d receptor splice variant shares functional properties with the other short isoforms of mGlu 1 receptor

Abstract

Three splice variants of the rat metabotropic glutamate receptor 1 (mGlu 1a, 1b and 1c receptors) have been characterized so far. All have the same sequence up to the 46th residue following the 7th transmembrane domain, followed by different carboxyl-terminal tails. Whereas mGlu 1b and mGlu 1c receptors possess a short intracellular carboxyl-terminal tail, the mGlu 1a receptor has a very long one. Compared to cells expressing mGlu 1b or mGlu 1c receptors, a higher agonist potency and basal phospholipase C activity were detected in cells expressing mGlu 1a receptors. Another variant with a short carboxyl-terminal tail, the HmGlu 1d receptor, has been recently isolated from human brain. Here we show that the mGlu 1d receptor variant also exists in the rat. Like all rat mGlu 1 receptor variants, the mGlu 1d receptor activates phospholipase C upon stimulation with mGlu 1 receptor agonists. Although the rank order of agonist potency is the same on mGlu 1a and mGlu 1d receptors, agonists are less potent in stimulating phospholipase C in mGlu 1d receptor-expressing cells than in cells expressing mGlu 1a receptors. Moreover, like the other short variants it has no significant constitutive activity. These results indicate that the mGlu 1d receptor shares similar functional properties with the other short mGlu 1 receptor splice variants, and further suggests that the long carboxyl-terminal tail of the mGlu 1a receptor increases phospholipase C coupling efficacy.