Ontogenesis of proenkephalin products in rat striatum and the inhibitory effects of low-level lead exposure.

Certain developmental abnormalities have been associated with environmental exposure to lead and our previous studies have indicated that the endogenous opioid system is disrupted by this metal. In connection with this we report the ontogeny of proenkephalin products in the rat striatum determined by combined HPLC and bioassay and the effects of low-level lead exposure on this ontogeny. The development of Met-enkephalin levels was dissimilar from that of the other proenkephalin products, Met-enkephalyl-Arg6-Phe7, Met-enkephalyl-Arg6-Gly7-Leu8 and Leu-enkephalin. The ratios of Met-enkephalin containing peptides to Leu-enkephalin was less than the 6:1 ratio predicted from the proenkephalin structure. Lead (administered in the maternal drinking water, from conception to weaning at 100, 300 and 1000 ppm) caused a dose-related depression of the levels of proenkephalin products in rat striatum at 10, 21 and 30 days after birth. The most pronounced effects were observed at 10 days and the most persistent effects were seen with Met-enkephalin. Peak blood lead levels were below 45 micrograms/100 ml in the 100 and 300 ppm lead-dosed groups and in all lead-dosed groups at 10 days after birth. It is suggested that lead may have inhibitory effects on proenkephalin-processing enzymes.