TRANSIENT EXPRESSION OF OPIOID RECEPTORS IN DEFINED REGIONS OF DEVELOPING BRAIN - ARE EMBRYONIC RECEPTORS SELECTIVE

The developmental profile of opioid receptors was studied in rat and guinea pig striatum and hippocampus. The two brain regions show different receptor profiles during development, which are characteristic for each animal. Yet, both tissues and animal species share one common feature; the binding of the universal opioid ligand [H-3]diprenorphine per milligram of protein is high at the early embryonic period, it decreases toward birth, and then gradually increases to the adult levels. This apparent transient expression of the receptors during the early developmental stage was manifested in the guinea pig as an actual decrease in the total receptor number. As an attempt to characterize the receptors involved in this process, the binding of the selective mu-opioid ligand [H-3]Tyr-D-Ala-Gly-MePhe-NH(CH2)OH ([H-3]DAGO) was studied in striatal membranes of young (P1) and adult (P60) rats. Competition between [H-3]DAGO and the delta-selective peptide Tyr-D-Pen-Gly-Phe-D-Pen (DPDPE) shows higher affinity of the delta-opioid to P1 membranes than to P60 membranes, though the number of delta-receptors in P1 membranes is very small. This observation is in line with a previous study suggesting that opioid receptors in embryonic striatum and hippocampus are less selective to various opioids than those of adult brain. An additional difference between adult and embryonic tissue was observed on Scatchard analysis of [H-3]DAGO binding; striatum P60 membranes exhibit one binding site with a K(D) of 0.8 +/- 0.1 nM and Hill coefficient of 0.96, whereas striatum P1 membranes bind the peptide in an apparent cooperative fashion with an overall Hill coefficient of 1.30. The possibility that a cooperative binding pattern involves interactions of SH groups was tested with the sulfhydryl reducing agent dithiothreitol (DTT). Indeed, DTT-treated membranes from adult rat striatum bind [H-3]DAGO in a cooperative fashion (Hill coefficient, 1.32). The significance of a transient expression of apparently nonselective opioid receptors in developing brain, and the possibility that receptors from embryonic and adult brain interact differently with one another or with other membrane constituents, such as G proteins and ion channels, is discussed.