PMID- 15351511
OWN - NLM
STAT- MEDLINE
DCOM- 20051108
LR  - 20131121
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 152
IP  - 2
DP  - 2004 Sep 17
TI  - Transiently overexpressed alpha2-adrenoceptors and their control of DNA synthesis 
      in the developing brain.
PG  - 233-9
AB  - During brain development, neurotransmitters act as trophic factors controlling 
      the patterns of cell replication and differentiation. Alpha2-adrenoceptors 
      (alpha2ARs) are transiently overexpressed in zones with high mitotic activity and 
      we evaluated whether these receptors are linked to DNA synthesis in the perinatal 
      rat brain. Acute administration of clonidine (2 mg/kg), an alpha2AR agonist, 
      elicited dramatic decreases in DNA synthesis in the forebrain, brainstem, and 
      cerebellum whether given on gestational day (GD) 21, or on postnatal days (PN) 1 
      or 8. However, alpha2AR blockade elicited by yohimbine (2.5 mg/kg) also resulted 
      in decreased DNA synthesis on GD21 and PN8, albeit to a smaller extent than with 
      clonidine. Yohimbine was able to blunt the effects of clonidine, verifying that 
      both drugs are acting through the same receptor population. Because betaARs are 
      also known to regulate DNA synthesis, we used propranolol (10 mg/kg) blockade of 
      betaARs to evaluate whether the alpha2AR effects were mediated by presynaptic 
      autoreceptors that regulate the release of norepinephrine and consequent betaAR 
      responses; the effects of yohimbine were still discernible in the presence of 
      propranolol. Accordingly, transiently overexpressed alpha2ARs in the developing 
      brain participate in the control of DNA synthesis in a biphasic manner, with 
      promotional actions at low, endogenous levels of stimulation, but inhibitory 
      effects when stimulation is high. Effects on alpha2ARs are likely to contribute 
      to long-term consequences of adrenergic agents used in obstetrics or 
      neurotoxicants that affect adrenergic activity.
FAU - Kreider, Marisa L
AU  - Kreider ML
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Box 3813, Durham, NC 27710, United States.
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Cousins, Mandy M
AU  - Cousins MM
FAU - Tate, Charlotte A
AU  - Tate CA
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - HD09713/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (Adrenergic alpha-2 Receptor Antagonists)
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Adrenergic beta-Antagonists)
RN  - 0 (Receptors, Adrenergic, alpha-2)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 9007-49-2 (DNA)
RN  - 9Y8NXQ24VQ (Propranolol)
RN  - MN3L5RMN02 (Clonidine)
SB  - IM
MH  - Adrenergic alpha-2 Receptor Agonists
MH  - Adrenergic alpha-2 Receptor Antagonists
MH  - Adrenergic alpha-Agonists/pharmacology
MH  - Adrenergic alpha-Antagonists/pharmacology
MH  - Adrenergic beta-Antagonists/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain/drug effects/*growth & development/*metabolism
MH  - Clonidine/pharmacology
MH  - DNA/*biosynthesis
MH  - Down-Regulation/drug effects/physiology
MH  - Drug Interactions/physiology
MH  - Propranolol/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, alpha-2/*metabolism
MH  - Up-Regulation/drug effects/physiology
MH  - Yohimbine/pharmacology
EDAT- 2004/09/08 05:00
MHDA- 2005/11/09 09:00
CRDT- 2004/09/08 05:00
PHST- 2004/07/08 00:00 [accepted]
PHST- 2004/09/08 05:00 [pubmed]
PHST- 2005/11/09 09:00 [medline]
PHST- 2004/09/08 05:00 [entrez]
AID - S0165-3806(04)00233-0 [pii]
AID - 10.1016/j.devbrainres.2004.07.001 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 2004 Sep 17;152(2):233-9. doi: 
      10.1016/j.devbrainres.2004.07.001.