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Title: Modulation of type 1a metabotropic glutamate receptor signalling by extracellular Ca²+
Author: Saunders, Ruth Mary
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2000
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This Thesis describes experiments in which the modulation of type 1 metabotropic glutamate receptor (mGluR1) signalling by [Ca2+]e has been studied. These experiments set out to investigate the Ca2+-sensitivity of mGluR1 expressed in a baby hamster kidney cell line. Increasing [Ca2+]e was demonstrated to enhance agonist-stimulated phosphoinositide signalling via mGluR1, but not the M3-muscarinic receptor, expressed in baby hamster kidney (BHK) cells, suggesting that the modulatory effect of Ca2+ is selective to signalling via mGluR1. The limitation of this modulatory effect of Ca2+e in BHK-S154A-mGluR1 lends support for the involvement of this region in the Ca2+ sensitivity of mGluRs. The ability of Ca2+ to modulate signalling via mGluR1 inducibly expressed in a Chinese hamster ovary (CHO) cell line, was then investigated. As in BHK cells increasing [Ca2+]e resulted in a graded increase in agonist-stimulated [3H]-InsP1 accumulation via mGluR1, not observed in CHO cells expressing the M3-muscarinic receptor, suggesting that the modulatory effect of [Ca2+]e is selective to signalling via mGluR1. Studies then investigated the site at which Ca2+e had its modulatory effect. Varying [Ca2+]e had no effect on membrane phospholipid levels. Measurement of [Ca2+]i elevation in different [Ca2+]e was not conclusive in determining the site of action of Ca2+. Manipulations of the levels of PKC and CaM in the cells suggest these proteins are not involved in the modulation of phosphoinositide signalling via mGluR1 by [Ca2+]e. Initial data provide evidence that the modulatory effect of Ca2+ on agonist-stimulated signalling via mGluR1 is, like the agonist activity of Ca2+ on mGluR1 expressed in Xenopus oocytes, dependent on the presence of the serine 166 residue. Further studies are required to confirm and extend these data.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available