KAPPA-OPIOID RECEPTORS STIMULATE PHOSPHOINOSITIDE TURNOVER IN RAT-BRAIN

The effects of various subtype-selective opioid agonists and antagonist on the phosphoinositide (Pl) turnover response were investigated in the rat brain. The κ-agonists U-50,488H and ketocyclazocine produced a concentration-dependent increase in the accumulation of IP's in hippocampal slices. The other κ-agonists Dynorphin-A (1-1-13) amide, and its protected analog D[Ala]2-dynorphin-A (1-13) amide also produced a significant increase in the formation of [3H]-lP's, whereas the μ-selective agonists [D-Ala2-N-Me-Phe4-Gly5-ol]-enkephalin and morphine and the δ-selective agonist [D-Pen2,5]-enkephalin were ineffective. The increase in lP's formation elicited by U-50,488H was partially antagonized by naloxone and more completely antagonized by the κ-selective antagonists nor-binaltorphimine and MR 2266. The formation of lP's induced by U-50,488H varies with the regions of the brain used, being highest in hippocampus and amygdala, and lowest in striatum and pons-medulla. The results indicate that brain κ- but neither μ- nor δ-receptors are coupled to the Pl turnover response. © 1990.