The rat mGlu1d receptor splice variant shares functional properties with the other short isoforms of mGlu1 receptor

Three splice variants of the rat metabotropic glutamate receptor 1 (mGlu1a, 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 mGlu1b and mGlu1c receptors possess a short intracellular carboxyl-terminal tail, the mGlu1a receptor has a very long one. Compared to cells expressing mGlu1b or mGlu1c receptors, a higher agonist potency and basal phospholipase C activity were detected in cells expressing mGlu1a receptors. Another variant with a short carboxyl-terminal tail, the HmGlu1d receptor, has been recently isolated from human brain. Here we show that the mGlu1d receptor variant also exists in the rat. Like all rat mGlu1 receptor variants, the mGlu1d receptor activates phospholipase C upon stimulation with mGlu1 receptor agonists. Although the rank order of agonist potency is the same on mGlu1a and mGlu1d receptors, agonists are less potent in stimulating phospholipase C in mGlu1d receptor-expressing cells than in cells expressing mGlu1a receptors. Moreover, like the other short variants it has no significant constitutive activity. These results indicate that the mGlu1d receptor shares similar functional properties with the other short mGlu1 receptor splice variants, and further suggests that the long carboxyl-terminal tail of the mGlu1a receptor increases phospholipase C coupling efficacy.