Lead toxicity and alterations in opioid systems

The opioid peptide system in the brain is probably the most extensive and diverse peptidergic transmission system. Three peptide precursors, pro-opiomelanocortin, proenkephalin and prodynorphin produce over 20 opioid peptides collectively known as the endorphins, enkephalins and dynorphins. Their effects are mediated by three receptors mu, delta and kappa, and the opioid system has control over several physiological functions including pain, locomotion, mood, diuresis, thermoregulation, stress, respiratory, gastrointestinal and cardiovascular function. Lead treatment (primarily using rat models) has shown that exposure to this metal in the perinatal period alters the development of endorphins and enkephalins, toxic effects which for the pro-opiomelanocortin products may be manifested at the gene level. Lead also alters the development of mu and delta receptors and biological responses to opioids such as analgesia, locomotion and stress responses. There are indications that the dynorphin/kappa opioid system is less affected than the mu and delta systems and this may suggest vulnerability to toxicity in the postnatal period as kappa systems are fully developed at birth whilst mu and delta systems are immature. In addition, hypothalamic and pituitary disruption of opioid peptides, plus alteration of stress-mediated activity by lead point to toxicity upon opioid controlled hormonal function. Comparative studies with other CNS neurochemicals and measures of blood lead levels suggest that opioid peptides are among the most sensitive neurotransmitter/neurohormonal systems to toxic insult by lead.