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Title: Pharmacology of the orphan opioid receptor
Author: Ho, M. T. B.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The neuropeptide nociceptin/orphanin FQ (OFQ) was recently identified as the endogenous agonist of the orphan opioid receptor ORL1. In this thesis pharmacological studies on the ORL1 receptor were advanced by the comparison of the potencies and efficacies of several ligands at the rat ORL1 receptor stably transfected into chinese hamster ovary (CHO) cells, with those at the native receptor in the central (frontal cortex) and peripheral (anococcygeus muscle) nervous systems. Most notably, the work involved a close examination of the pharmacology of the first selective non-peptide antagonist for the ORL1 receptor, J-113397, and in this case the work extended to the use of in-vivo techniques measuring effects on locomotor activity and food consumption. The work on the pharmacology of the ORL1 receptor in the anococcygeus followed our discovery of the presence of the receptor in this tissue. Under conditions where electrical-field stimulation produced a selective activation of the sympathetic nerves, nociceptin/OFQ fully inhibited the pure adrenergic motor response. The hexapeptides Ac-RYYRWK-NH2 (RWK) and Ac-RYYRIK-NH2 (RIK) were potent partial-agonists whereas [Phe1ψ(CH2-NH)Gly2]nociceptin(1-13)NH2 (FGNC13) and J-113397 had little or no efficacy and were competitive antagonists. This thesis reflects on the various pharmacological actions of nociceptin/OFQ, concentrating on establishing discriminatory effects for selected compounds and possible functional role of the ORL1 receptor in the brain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available