Eect of bupropion on immunodensity of putative imidazoline receptors on platelets of depressed patients He Zhu a , Angelos Halaris a , Sudhakar Madakasira a, 1 , Peggy Pazzaglia a , Nancy Goldman a , C. Lindsay DeVane d , Mike Andrew e , Donald Reis f , John E. Piletz a±c, * a Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA b Department of Pharmacology and Toxicology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA c Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA d Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA e Department of Preventative Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA f Division of Neurobiology, Department of Neurology and Neurosciences, Cornell University Medical College, New York, NY, USA Received 1 August 1998; received in revised form 15 February 1999; accepted 23 February 1999 Abstract A substantial number of studies have demonstrated increased imidazoline receptors (I 1 binding sites) on platelets of depressed patients and downregulation following antidepressant treatments. Herein, imidazoline receptor binding protein (IRBP) antiserum was used to quantify imidazoline receptors on platelets of depressed patients before and after treatment with the atypical aminoketone antidepressant, bupropion. Western blots revealed an increase in IRBP-immunodensity ( p=0.01, two-tailed) in a 33 kDa protein band in untreated depressed patients (n=21) as compared with controls (n=17). This band has been positively correlated with I 1 binding sites on platelets. Following 6 weeks' treatment with bupropion, IRBP-immunodensity was downregulated in depressed patients ( p=0.03, paired t-test); predominantly in responders ( p=0.005). Patients non-responsive to bupropion (n=5) were signi®cantly dierent from responders ( p=0.05) by exhibiting no elevation in IRBP-immunodensity at pre-treatment and no downregulation of the 33 kDa band after treatment. IRBP-immunodensity was negatively correlated (r= À 0.79, p=0.01) with plasma concentrations of bupropion and its metabolites at week-4 of BUP treatment. Thus, a 33-kDa IRBP on platelet plasma membranes is elevated in depression and normalized in responders to bupropion. # 1999 Elsevier Science Ltd. All rights reserved. Keywords: Antidepressant; Depression; Imidazoline receptors; Immunoreactivity; CD61; Platelets; Downregulation; Antiserum; Bupropion; Clo- nidine 1. Introduction Non-adrenergic imidazoline binding sites (I-sites) have been well characterized using radioligands like [ 3 H]-clonidine (Ernsberger et al., 1995a; Parini et al., 1996). I-sites are dispersed throughout the brain in a manner distinct from a 2 -adreonoceptors (DeVos et al., 1994) and clonidine-related compounds possess a- nities at these sites which correlate with their anti- hypertensive potencies when applied centrally (Buccafusco et al., 1995; Molderings, 1997). In ad- dition, a number of psychopharmacological function(s) have been suggested for imidazoline receptors (IR) (Piletz et al., 1995b). At least two I-sites, I 1 and I 2 , have been de®ned based on dierential binding a- nities, subcellular localizations and regional brain dis- Journal of Psychiatric Research 33 (1999) 323±333 0022-3956/99/$ - see front matter # 1999 Elsevier Science Ltd. All rights reserved. PII: S0022-3956(99)00009-6 1 Present address: 4500 I-55 North, 234 Highland Village, Jackson, MS 39211, USA. * Corresponding author. Tel.: +1-601-984-5898; fax: +1-601-984- 5899. E-mail address: jepil@®ona.umsmed.edu (J.E. Piletz)