A COMPARISON OF 2 ALTERNATIVELY SPLICED FORMS OF A METABOTROPIC GLUTAMATE-RECEPTOR COUPLED TO PHOSPHOINOSITIDE TURNOVER

A comparison of the pharmacological and physiological properties of th e metabotropic glutamate 1alpha and 1 beta receptors (mGluR1alpha and mGluR1beta) expressed in baby hamster kidney (BHK 570) cells was perfo rmed. The mGluR1beta receptor is an alternatively spliced form of mGlu R1alpha with a modified carboxy terminus. Immunoblots of membranes fro m the two Gell lines probed with receptor-specific antipeptide antibod ies showed that mGluR1alpha migrated with an M(r) = 154,000, whereas m GluR1beta migrated with an M(r) = 96,000. Immunofluorescence imaging o f receptors expressed in BHK 570 cells revealed that the mGluR1alpha r eceptor was localized to patches along the plasmalemma and on intracel lular membranes surrounding the nucleus, whereas mGluR1beta was distri buted diffusely throughout the cell. Agonist activation of the mGluR1a lpha and the mGluR1beta receptors stimulated phosphoinositide hydrolys is. At both receptors, glutamate, quisqualate, and ibotenate were full agonists, whereas trans-(+)-1-aminocyclopentane-1,3-dicarboxylate app eared to act as a partial agonist. The stimulation of phosphoinositide hydrolysis by mGluR1alpha showed pertussis toxin-sensitive and insens itive components, whereas the mGluR1beta response displayed only the t oxin-insensitive component. The mGluR1alpha and mGluR1beta receptors a lso increased intracellular calcium levels by inducing release from in tracellular stores. These results indicate that the different carboxy terminal sequences of the two receptors directly influences G protein coupling and subcellular deposition of the receptor polypeptides and s uggest that the two receptors may subserve different roles in the nerv ous system.