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Title: A study of NK-3 tachykinin receptors
Author: Guard, Steven
ISNI:       0000 0001 3521 6723
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 1989
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The aim of this thesis was to determine the pharmacological characteristics and biochemical properties of NK-3 tachykinin receptors in the mammalian central nervous system (cerebral cortex and spinal cord) and periphery (guinea-pig ileum; GPILM). The affinities of naturally-occurring tachykinins and several receptorselective analogues, for peripheral (GPILM) and central (guinea-pig cortex) NK-3 receptors (labelled with the selective NK-3 receptor ligand, [3H]-senktide) have been determined. A good correlation between affinities of the above peptides for NK-3 sites in the two tissues was obtained. The inhibition of [3H]-senktide binding by guanine nucleotides, in addition to the correlation between affinities of tachykinins at NK-3 sites and their biological potencies in contracting the rat portal vein (RPV; data from the literature), suggest that [3H]-senktide binding sites represent functional receptors. Evidence for the coupling of GPILM and neonatal rat spinal cord (but not RPV or rat cerebral cortex) NK-3 receptors, to the hydrolysis of inositol phospholipids has been obtained. In GPILM, morphine was found to inhibit the formation of [3H]-inositol phosphates in response to the NK-3 agonist, senktide. This finding is in agreement with the hypothesis that the indirect contractile action of tachykinins in GPILM is due to the activation of neuronal NK-3 receptors and the release of acetylcholine (ACh). This idea has also been confirmed by contractile and [3H]-ACh release studies. Autoradiographical studies in spinal cord, using [3H]-senktide, have shown the presence of NK-3 sites in the dorsal horn. These findings, taken together with the recent report that NK-3 agonists may be analgesic, suggest that the guinea-pig ileum might be a useful bioassay for the evaluation of potent and selective NK-3 agonists which may represent novel analgesic agents.
Supervisor: Watson, Steve P. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Tachykinins ; Central nervous system