The existence of opioid receptor subtypes would be consistent with the discoveries of multiple muscarinic, adrenergic, and serotonergic receptor subtypes and would provide new opportunities for opioid pharmacology. these opportunities would result from the presence of new receptor targets for opioid drug development. It may be possible to show that certain opioid receptor subtypes mediate desirable effects like analgesia without mediating dangerous effects like respiratory depression. The focus of this proposal concerns the identification and characterization of mu and delta opioid receptor heterogeneity.
The specific aims of this proposal are: 1. To test our hypothesis that there are at least two subtypes of the delta opioid receptor by the examination of their ligand binding properties using our recently developed radiolabeled radioligands. 2. To use radioligand binding methods to test hypotheses related to the mu- delta opioid receptor complex. these hypotheses include: A. That DPDPE acts at a mu opioid receptor coupled delta opioid receptor through an allosteric mechanism that serves to potentiate mu opioid agonist-induced analgesia in the brain. B. That the enkephalin analogue DALCE selectively antagonizes the delta opioid receptor acted upon by DPDPE but not that of the highly delta selective agonist deltorphin II. C. That the isothiocynante derivative of naltrindole (NTII) selectively blocks the receptor responsible for deltorphin II induced analgesia but does not recognize the delta opioid site acts upon by DPDPE. D. That D-Tca-CTAP where D-Tca is an analogue of D-Trp and a novel bivalent enkephalin analogue biphalin act at coupled mu and delta opioid receptors through a self-potentiation mechanism.
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