on March 11, 2004
Published online before print March 11, 2004, doi: 10.1161/01.STR.0000121644.82596.7e
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Submitted on August 29, 2003
From the Laboratory for Psychoneuroimmunology (M.S.L., E.v.d.T., A.K., C.J.H.) and the Department of Neonatology (E.v.d.T., F.G., F.v.B.), University Medical Center Utrecht, Utrecht, Netherlands. * To whom correspondence should be addressed. E-mail: c.heijnen{at}azu.nl.
Background and Purpose--Neurotransmitters, neuropeptides, chemokines, and many other molecules signal through G protein-coupled receptors (GPCRs). GPCR kinases (GRKs) and Materials and Methods--Twelve-day-old rat pups were exposed to 90 minutes of hypoxia (fraction of inspired oxygen [FiO2] 0.08) after ligation of the right carotid artery, a procedure that induces unilateral damage in the right hemisphere. At 6, 12, 24, and 48 hours after HI, the left (hypoxic) and right (hypoxic/ischemic) hemispheres were analyzed for GRK and Results--HI downregulated GRK2 protein expression in both hemispheres at 24 to 48 hours after HI, and the effect was more pronounced in the ipsilateral hemisphere. HI induced no global change in GRK6 protein expression. However, GRK2 was markedly decreased in the hippocampal region of the ipsilateral hemisphere that will be severely damaged after HI. No changes in global mRNA levels for GRK2 were detected. In contrast, HI increased Conclusions--Neonatal HI-induced brain damage is associated with specific changes in the GPCR desensitization machinery. We hypothesize that these changes result in supersensitization of multiple GPCRs and might therefore contribute to HI-induced brain damage.
Revised on November 26, 2003
Accepted on January 5, 2004
Hypoxia/Ischemia Modulates G Protein-Coupled Receptor Kinase 2 and
Maria Stella Lombardi PhD; 
-Arrestin-1 Levels in the Neonatal Rat Brain
-arrestins play a crucial role in regulating the responsiveness of multiple GPCRs. Reduced expression of GRK and -arrestins leads to supersensitization of GPCRs and will thereby increase the response to neuropeptides and neurotransmitters. We analyzed GRK and -arrestin expression after cerebral hypoxia/ischemia (HI).-arrestin protein and mRNA expression by Western blotting and real-time polymerase chain reaction, respectively. In addition, we analyzed GRK2 expression in the hippocampus by immunohistochemistry.-arrestin-1 protein expression as well as mRNA levels at 6 to 12 hours after HI.
Key words: hypoxia • ischemia • newborn • receptors, G-protein coupled
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