OPIOID DELTA SUBTYPES: CORRELATION IN VITRO AND IN VIVO

The specific goals of the proposed work are to (a) directly identify
opioid delta receptor subtypes in brain and other tissues using
radioligand binding techniques in wholebrain control membranes, in
membranes pretreated with selective and irreversible ligands, in
membranes from different strains of mice which have been reported to show
differences in populations of opioid receptors (e.g., the mu-receptor
deficient CXBK mouse), and in membranes from specific brain regions; (b)
investigate possible differences in the regulation of interactions of the
receptor subtypes with their respective effector systems by evaluation
of radioligand binding in the presence of guanine nucleotides, cations
(or both), or following pretreatment with pertussis toxin in vitro or in
vivo; (c) use radioligand binding techniques to evaluate possible
mechanism of tolerance and supersensitivity following repeated/continuous
exposure of the brain to compounds with selectivity for the opioid delta
receptor subtypes, and (d) use some of the above approaches in an
effector system by measuring adenylyl cyclase activity in NG 108-15
cells. Such approaches will provide insights into opioid delta subtypes,
and their mechanisms which may correlate with substantial data
accumulated in vivo, and may be important in establishing the potential
therapeutic utility of delta subtype selective drugs.