DISSOCIATION BETWEEN THE INHIBITORY AND STIMULATORY EFFECTS OF OPIOID-PEPTIDES ON CAMP FORMATION IN SK-N-SH NEUROBLASTOMA-CELLS

Opioid agonists either potentiate or suppress basal cAMP production in SK-N-SH cells. The inhibitory effect is mediated by PTX-sensitive GTP -binding proteins, while the stimulatory effect involves Ca++ entry an d calmodulin activation. Both pathways can be activated simultaneously by opioid agonists. Low (nM) concentrations of either mu (DAMGO) or d elta (DPDPE) selective opioids potentiate cAMP formation. At higher (1 00nM) concentrations, however a met suppression takes over; this suppr ession can be eliminated by PTX, and the underlying stimulatory effect is disclosed. Micromolar concentrations of either mu or delta selecti ve agonists cross-activate the other (delta or mu) receptors, and augm ent the stimulatory pathway. The overall outcome (either stimulation o r inhibition of cAMP production) is dependent on the balance between t he two overlapping-pathways, and can be modified by blocking either of the two opposing mechanisms. (C) 1998 Academic Press.