Perinatal lead exposure alters the development of delta- but not mu-opioid receptors in rat brain.
1. Low level lead exposure has been shown to impair the development of opioid peptide levels in the brain, and to impair antinociceptive responses to opioid drugs. We have now studied the effects of lead exposure on the development of opioid receptors using ligand binding studies. 2. The ontogenesis of mu- and delta-opioid binding sites was studied using rat whole brain membranes and [3H]-[D-Ala2MePhe4-Gly-ol]enkephalin and [3H]-[D-Pen2,D-Pen5]enkephalin as binding ligands. Rats were exposed to lead during development by addition of lead acetate (at 100-1000 p.p.m.) to the maternal drinking water from conception to postnatal day 14. 3. Perinatal lead exposure had no significant effects on the binding affinity (KD) or binding capacity (Bmax) for the mu-opioid receptor measured at postnatal days 10, 21 and 30. Lead exposure (at 1000 p.p.m.) increased the KD for the delta-opioid receptor at postnatal days 15, 21, 35 and 50 but had no effect on the binding capacity. No indications of overt toxicity were observed and blood lead levels were in the ranges considered to represent subclinical lead toxicity in man. 4. The lack of effect of lead on mu-receptor binding contrasts with previously described impairment of antinociceptive effects of mu-agonists suggesting that the toxicity is not manifested at the mu-binding site. However, the delta-opioid receptor appears to be more sensitive to lead exposure and the persistent changes in delta-site affinity after cessation of lead exposure suggest irreversible damage in the production of the receptor protein.
McDowell
J
J
Department of Biochemistry, University of Surrey, Guildford.
Kitchen
I
I
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007854:Lead / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D007854:Lead