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

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 shea 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. (C) 1997 Elsevier Science B.V.