Alterations in beta-adrenergic receptor density and adenylate cyclase activity in the rat brain treated chronically with lead.
Behavioral and memory impairment resulting from lead exposure is well known but the mechanism is not. We utilized the brain of lead exposed rats to investigate this problem. In an effort to elucidate the mechanism responsible for this alteration we examined blood and brain lead levels, brain beta-adrenoceptor density and cyclic AMP production in lead exposed rats. Wistar rats used in these trials were divided into six groups of ten animals each. Five groups were given drinking water containing 0.05, 0.1, 0.5, 1 and 2% lead acetate for a period of 60 days. One group (control group, 0% lead acetate) was given pure water. Application of a trend test indicated that both blood and brain lead levels increased significantly from group 0% to group 2% (group 0% <group 0.05% <group 0.1% <group 0. 5%<group 1%<group 2%), but that brain beta-adrenoceptor density and cyclic AMP levels stimulated by isoproterenol decreased (group 2%<group 1%<group 0.5%<group 0.1%<group 0.05%<group 0%). Kd did not vary among the six groups and this indicated that the affinity of the remaining beta-adrenoceptors for [125I]iodocyanopindolol was not changed. Linear regression analysis showed that beta-adrenoceptor density and stimulated cyclic AMP level in brain was found to be negatively correlated with brain lead level (P<0.001). The results show lead exposure that may be the result of an alteration of beta-adrenergic receptor and adenylate cyclase activity in brain.
Tsao
D A
DA
Institute of Biomedical Sciences Academia Sinica, Taipei City, Taiwan.
Yu
H S
HS
Cheng
J T
JT
Ho
C K
CK
Chang
H R
HR
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D001923:Brain Chemistry / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D020120:Iodocyanopindolol; D007854:Lead / Q000097:blood; D020263:Lead Poisoning, Nervous System / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011524:Protoporphyrins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012044:Regression Analysis; D015032:Zinc / Q000097:blood
D011524:Protoporphyrins; D011943:Receptors, Adrenergic, beta; D007854:Lead; D020120:Iodocyanopindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015032:Zinc