The lymphoblast beta-adrenergic receptor in bipolar depressed patients: characterization and down-regulation.
beta-Adrenergic receptor binding and adenylyl cyclase activity were examined in lymphoblast cell lines established from 12 patients with bipolar disorder and 10 unrelated healthy control subjects. No significant differences were found in [125I]iodocyanopindolol binding affinity or capacity or in isoprenaline-stimulated cAMP response. Incubation of lymphoblasts with isoprenaline (1 nM) for 24 h prior to assay reduced both receptor number and adenylyl cyclase activity. The extent of receptor down-regulation was significantly less in cells of bipolar disorder patients (20 +/- 5%) compared to controls (40 +/- 4%). Desensitization of adenylyl cyclase, however, was reduced to a similar degree in bipolar (65 +/- 14%) and control (68 +/- 20%) subjects. We conclude that basal beta-adrenergic receptor characteristics are not altered in bipolar disorder but that agonist down-regulation of receptor number may be less efficient than in control cells. The functional implications of this effect are discussed.
Department of Pharmacology, St. Mary's Hospital Medical School, London, UK.
G
G
Kay
M
M
Sargeant
P
P
McGuffin
S
S
Whatley
R
R
Marchbanks
D
D
Baldwin
S
S
Montgomery
J M
JM
Elliott
D000262:Adenylyl Cyclases / Q000502:physiology; D000328:Adult; D001714:Bipolar Disorder / Q000503:physiopathology*; D002460:Cell Line; D000242:Cyclic AMP / Q000097:blood; D015536:Down-Regulation; D005260:Female; D006801:Humans; D020120:Iodocyanopindolol; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D010869:Pindolol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases