P. Delay-Goyet, M. Ruiz‐Gayo, A. Baamonde
Jan 31, 1991
Citations
1
Influential Citations
18
Citations
Quality indicators
Journal
Pharmacology Biochemistry and Behavior
Abstract
Abstract The peptidase-resistance and bioavailability of BUBU [H-Tyr-D.Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu)-OH], a highly selective and potent agonist of the δ opioid receptor, have been investigated in vitro and in vivo. In vitro at 37°C, the peptide was fully resistant to degradation by rat serum and strongly resistant to degradation by rat brain membrane. In vivo 0.065% of the dose of [ 3 H]BUBU injected intravenously to the mouse was present 15 min later in the brain. The percentage determined for [ 3 H]DAGO [H-Tyr-D.Ala-Gly-(NMe)Phe-Gly-ol], a selective ligand for μ sites, was 0.038%. Specific binding to mouse brain membranes, determined after intracerebroventricular injection of [ 3 H]BUBU, was saturable and a high affinity (K D app =25 pmol) was evaluated for the δ-agonist. Competition experiments showed that BUBU is a selective ligand for δ receptors in vivo. Comparison of the analgesic potency (hot plate test) of ICV or IV administered increasing doses of BUBU and DAGO with their in vivo binding properties supports the preferential involvement of μ receptors in supraspinal analgesia. BUBU also induced an increase in spontaneous locomotion after IV administration at a dose lower than that which produced analgesia. The quantitative results obtained in the present study demonstrate that BUBU and DAGO could be used to characterize the pharmacological responses induced by selective stimulation of δ and μ receptors after systemic administration.