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Title: The functions of inducible recombinant somatostatin receptors and those of native receptors in the rat trigeminal ganglion
Author: Cole, S. L.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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Somatostatin (SRIF) is a peptide with a multiplicity of effects in the central nervous system and the periphery. It induces its effects by activating a family of five G protein-coupled receptors, (sst1-sst5). The consequence of SRIF receptor activation is routinely studied using recombinant cell lines that characteristically express high levels of receptor. The objectives of this study were to determine how changes in receptor expression alter the operational characteristics of the receptor and to compare these with responses obtained following activation of SRIF receptors expressed endogenously in the rat trigeminal ganglion (TG). Using an ecdysone inducible expression system, a time- and concentration-dependent induction of sst2 receptor expression was attained by exposure of CHO-K1 cells to the inducing agent, muristerone A (MuA). Maximal sst2 receptor expression was achieved after treatment of the cells with 7mM MuA for 24 hours. Exposure of the cells to SRIF led to the concentration-dependent inhibition of adenylate cyclase in addition to time-dependent increases in the level of MAP kinase phosphorylation. The activation of both of these signalling pathways was shown to correlate with the degree of sst2 receptor inductor. However, fluorescence-activated cell sorting analysis demonstrated that over prolonged time periods, stable consistent expression of the sst2 receptor could not be maintained in CHO-K1 cells using this expression system. Hence, whilst the ecdysone inducible expression system was a useful tool to modulate functional sst2 receptor expression in a recombinant system, it was only appropriate for use over short time periods. To examine SRIF receptor activation in a native cell environment, primary TG neuronal cultures were used. The TG is the major sensory ganglion implicated in migraine headache and in the clinic, SRIF (and analogues) have been shown to have analgesic effects. Studies using RT-PCR and Western analysis demonstrated the presence of all five SRIF receptor types and SRIF itself in both adult and neonatal TG neurones.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available