Blunted beta-adrenergic responsivity of peripheral blood mononuclear cells in endogenous depression. Isoproterenol dose-response studies.
Previous studies of peripheral blood mononuclear cells isolated from drug-free, hospitalized patients with endogenous major depression have demonstrated a diminished adenosine 3',5'-monophosphate (cyclic AMP) response to single concentrations of isoproterenol as compared with that obtained from normal control subjects. We now report results of isoproterenol dose-response studies that indicate lower basal levels of cyclic AMP as well as diminished cyclic AMP levels in response to isoproterenol stimulation at concentrations ranging from 10(-10) to 10(-5) mol/L in drug-free, hospitalized patients with endogenous depression. The major factor responsible for the diminished cyclic AMP production in the depressed patients was a loss of receptor sites capable of cyclic AMP production. Taken together with our previously reported finding that beta-adrenergic antagonist binding was normal in peripheral blood mononuclear cells obtained from depressed patients, the results of the dose-response studies suggest a loss of receptor function (desensitization) rather than a diminished number of receptor binding sites (down-regulation) as the underlying mechanism. Potential explanations for beta-adrenergic desensitization and its implications for the catecholamine hypothesis of depressive disorders are discussed.
Halper
J P
JP
Department of Psychiatry, Cornell University Medical College, New York, NY 10021.
Brown
R P
RP
Sweeney
J A
JA
Kocsis
J H
JH
Peters
A
A
Mann
J J
JJ
D000328:Adult; D000368:Aged; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D003866:Depressive Disorder / Q000097:blood* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006760:Hospitalization; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol