Asymmetric modulation of a catecholamine-regulated protein in the rat brain, following quinpirole administration.
We previously reported a brain-specific 40 kDa catecholamine-regulated protein (CRP40) that binds dopamine (DA) and related catecholamines. CPR40 shares significant sequence homology with human heat shock protein (Hsp70), GRP78/BIP, and human #BQ24193 protein. Recent studies with the DA D(2) receptor antagonist, haloperidol, demonstrated a significant increase in expression of CRP40 in the striatum (STR). The objective of the present study was to investigate CRP40 expression in various brain regions following treatments with the DA D(2)/D(3) receptor agonist quinpirole (QNP) in rats and examine possible relationships between neurochemical parameters and locomotor activity. Rats received injections of either QNP (0.5 mg/kg, for 27 days every third day) or saline (SAL) and their locomotor activities were measured for 90 min after each injection. At injection 9, QNP-treated rats showed locomotor activity that was significantly greater than SAL controls (F(2,28) = 3.88, P < 0.05, Duncan's multiple range test, P < 0.05). Neurochemically, acute QNP-treated rats demonstrated significant differential expression of CRP40 in the left/right prefrontal cortex (PFC) relative to SAL-treated rats (-17.76 +/- 2.10%, -10.35 +/- 1.23%, P < 0.001). Chronic QNP significantly decreased CRP40 expression in the STR, ventral tegmental area (VTA), and left/right PFC (-24.85+/- 2.10%, -18.15 +/- 5.64%, -49.13 +/- 7.05%, -25 +/- 3.63%, P < 0.001). Finally, chronic QNP treatment resulted in a significant increase in CRP40 levels in the nucleus accumbens (NA) (+39.32 +/- 7.00%, P < 0.001). Heat shock protein (i.e., Hsp70 or Hsc70) expression remained unaltered following QNP treatment. Since QNP is a DA D(2)/D(3) agonist, alterations in CRP40 expression following QNP treatment suggest the protein's function in dopaminergic neurotransmission.
Gabriele
Joseph
J
Department of Psychiatry and Behavioral Neuroscience, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada, L8N 3Z5.
Culver
Kirsten
K
Sharma
Sunjay
S
Zhang
Bingjun
B
Szechtman
Henry
H
Mishra
Ram
R
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans
D018491:Dopamine Agonists; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D009419:Nerve Tissue Proteins; C422207:catecholamine-regulated protein, 40 kDa; D019257:Quinpirole