Dynorphin a to apparent k opioid receptors in deep layers of guinea pig cerebral cortex

Dynorphin A and its fragments (e.g. dynorphin A-(1-13)) potently displace prototypical alkaloid ligands for the ~ subtype of opioid receptor in rat (Quirion and Pert, 1981) and guinea pig (Chavkin et al., 1982; Corbett et al., 1982) brain membranes. However, we and others (Quirion and Pert, 1981; Corbett et al., 1982) have found that dynorphin A-related peptides also exhibit substantial potency in displacing prototypical/~ and 6 receptor ligands from brain membranes. Since these ligands are not completely selective, it is difficult to distinguish whether dynorphin acts at the/~ and 8 sites or if the radioligands bind to the K receptor. This issue has been clarified for guinea pig brain: [3H]dynorphin A binds specifically to guinea pig brain membranes and appears to selectively label x sites (Young et al., 1983). These sites, when labelled by [3H]ethylketocyclazocine or [3H]bremazocine, are concentrated in the deep layers of guinea pig cerebral cortex (Goodman and Snyder, 1982). Since these tritiated alkaloids exhibit little receptor selectivity, excess concentrations of ~ and ~ ligands are included in the incubation medium to ensure that only x sites are available for labelling (Corbett et al., 1982; Goodman and Snyder, 1982). However, the concentration of morphine (30 nM) used by Goodman and Snyder (1982) may have been insufficient to saturate the /~ sites (cf. Corbett et al., 1982). Since [3H]dynorphin A exhibits high x selectivity in guinea pig brain (Young et al., 1983), we carried out the present study to determine whether specific binding sites for this ligand are distributed in the deep cortical layers.