PMID- 11718842
OWN - NLM
STAT- MEDLINE
DCOM- 20020204
LR  - 20190901
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 131
IP  - 1-2
DP  - 2001 Nov 26
TI  - Beta-adrenoceptor signaling in the developing brain: sensitization or 
      desensitization in response to terbutaline.
PG  - 113-25
AB  - Beta(2)-adrenoceptor agonists are commonly used to arrest preterm labor but they 
      also penetrate the placenta to stimulate fetal beta-adrenergic receptors 
      (betaAR), and have been implicated in subsequent neurobehavioral deficits. We 
      administered terbutaline to pregnant rats on gestational days (GD) 17-20 and 
      during two postnatal (PN) periods, PN2-5 and PN11-14, that correspond to third 
      trimester human neurological development. We then examined betaAR binding sites 
      and adenylyl cyclase (AC) signaling in fetal brain or neonatal brain regions. 
      Although fetal terbutaline administration evoked betaAR downregulation, the 
      ability of isoproterenol to stimulate AC was enhanced instead of desensitized. 
      Sensitization occurred at post-receptor signaling proteins, as augmented 
      responses were also seen for stimulants that bypass the receptors to work on 
      G-proteins (NaF) or that stimulate AC directly (forskolin and Mn(2+)). When 
      terbutaline was given on PN2-5, betaAR downregulation was obtained in brainstem, 
      forebrain and cerebellum, but desensitization of the AC response was seen only in 
      the forebrain; the desensitization was heterologous, reflecting decrements in 
      total AC activity rather than specific loss of the betaAR response. With 
      treatment on PN11-14, only the cerebellum showed betaAR downregulation and 
      induction at the level of post-receptor signaling proteins maintained the 
      betaAR-mediated AC response. Our results indicate that, unlike the adult, betaAR 
      signaling in the fetus and neonate is resistant to homologous desensitization by 
      beta-agonists, and in fact, displays heterologous sensitization that sustains or 
      enhances the overall response. The inability to desensitize betaAR responses may 
      lead to disruption of neural cell development as a consequence of tocolytic 
      therapy.
FAU - Slotkin, T A
AU  - Slotkin TA
AD  - Box 3813 DUMC, Department of Pharmacology and Cancer Biology, Duke University 
      Medical Center, Durham, NC 27710, USA. t.slotkin@duke.edu
FAU - Tate, C A
AU  - Tate CA
FAU - Cousins, M M
AU  - Cousins MM
FAU - Seidler, F J
AU  - Seidler FJ
LA  - eng
GR  - HD 09713/HD/NICHD NIH HHS/United States
PT  - Journal Article
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 beta-Agonists)
RN  - 0 (Receptors, Adrenergic, beta)
RN  - 0 (Tocolytic Agents)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - N8ONU3L3PG (Terbutaline)
SB  - IM
MH  - Adaptation, Physiological/drug effects
MH  - Adenylyl Cyclases/metabolism
MH  - Adrenergic beta-Agonists/*pharmacology
MH  - Animals
MH  - Brain/drug effects/*growth & development/*metabolism
MH  - Cyclic AMP/metabolism
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Homeostasis/drug effects/physiology
MH  - Male
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Adrenergic, beta/*metabolism
MH  - Signal Transduction/*drug effects/physiology
MH  - Terbutaline/*pharmacology
MH  - Tocolytic Agents/pharmacology
EDAT- 2001/11/24 10:00
MHDA- 2002/02/05 10:01
CRDT- 2001/11/24 10:00
PHST- 2001/11/24 10:00 [pubmed]
PHST- 2002/02/05 10:01 [medline]
PHST- 2001/11/24 10:00 [entrez]
AID - S0165380601002826 [pii]
AID - 10.1016/s0165-3806(01)00282-6 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 2001 Nov 26;131(1-2):113-25. doi: 
      10.1016/s0165-3806(01)00282-6.