The lymphoblast beta-adrenergic receptor in bipolar depressed patients: effect of chronic incubation with lithium chloride.
We have recently reported a study of beta-adrenergic receptor binding characteristics in lymphoblast cell lines derived from patients with bipolar disorder (BD) and healthy, matched control subjects. In the present study we have investigated the effects of incubating cells from the same subjects with lithium chloride (1 mM) for 7 days prior to assay. There was no difference in beta-adrenergic receptor number between control and BD cell lines and incubation with lithium had no effect on receptor number in either group. Exposure of the cells to isoprenaline (1 nM) for 24 h immediately prior to assay caused significantly less down-regulation in BD cells (15 +/- 5%) than control cells (39 +/- 4%), as described previously. Incubation with lithium significantly increased the down-regulation response to isoprenaline in BD cells (39 +/- 6%) but not in control cells (30 +/- 7%). After lithium, the agonist-induced decrease in beta-AR number in BD cells was no longer significantly different from that in control cells. We conclude that lithium selectively enhanced the agonist down-regulation of beta-adrenergic receptors in cells derived from patients with bipolar disorder. The functional significance of this result and the potential biochemical mechanisms responsible for this effect are discussed.
Kay
G
G
Department of Pharmacology, St. Mary's Hospital Medical School, London, UK.
Sargeant
M
M
McGuffin
P
P
Whatley
S
S
Marchbanks
R
R
Bullock
T
T
Montgomery
S
S
Elliott
J M
JM
D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000503:physiopathology*; D002461:Cell Line, Transformed; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D018021:Lithium Chloride; D007545:Isoproterenol