PMID- 8069672
OWN - NLM
STAT- MEDLINE
DCOM- 19940923
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 646
IP  - 2
DP  - 1994 May 23
TI  - Steroid modulation of GABAA receptors in an amphibian brain.
PG  - 258-66
AB  - Steroids can modulate gamma-aminobutyric acid (GABAA) receptor function in rat 
      brains, but the physiological relevance of this mechanism is still unclear. To 
      determine whether this phenomenon is widespread among vertebrates, we 
      investigated steroid modulation of GABAA receptors in amphibian brain tissue. 
      Equilibrium binding parameters for t-butylbicyclophosphorothionate ([35S]TBPS) 
      and [3H]flunitrazepam were similar in Taricha granulosa and mammalian brains, as 
      was the allosteric regulation of [35S]TBPS and [3H]flunitrazepam binding by GABA. 
      The rank order and absolute potencies of steroids to inhibit [35S]TBPS binding 
      and enhance [3H]flunitrazepam binding were also similar in Taricha and rat 
      brains. As in mammalian studies, physiological concentrations of corticosterone 
      had no effect on ligand binding or GABA-stimulated Cl- uptake. In 
      autoradiographic studies, 3 alpha-hydroxy-5 alpha-pregnan-20-one inhibited 
      [35S]TBPS binding sites in all brain regions examined, whereas corticosterone had 
      no effect on [35S]TBPS binding. These studies suggest that the steroid 
      recognition sites on GABAA receptors have been highly conserved through 
      vertebrate evolution and thus portend physiologically important functions. 
      However, the pharmacological profiles for the GABAA receptor and the 
      high-affinity corticosteroid receptor are apparently different, suggesting there 
      are multiple types of steroid recognition sites on neuronal membranes.
FAU - Orchinik, M
AU  - Orchinik M
AD  - Department of Zoology, Oregon State University, Corvallis 97331.
FAU - Murray, T F
AU  - Murray TF
FAU - Moore, F L
AU  - Moore FL
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Bridged Bicyclo Compounds)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Chlorides)
RN  - 0 (Convulsants)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Steroids)
RN  - 0 (Sulfur Radioisotopes)
RN  - 04Y4D91RG0 (pregnenolone sulfate)
RN  - 10028-17-8 (Tritium)
RN  - 620X0222FQ (Flunitrazepam)
RN  - 70636-86-1 (tert-butylbicyclophosphorothionate)
RN  - 73R90F7MQ8 (Pregnenolone)
RN  - BXO86P3XXW (Pregnanolone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Autoradiography
MH  - Brain/drug effects/*metabolism
MH  - Bridged Bicyclo Compounds/metabolism
MH  - *Bridged Bicyclo Compounds, Heterocyclic
MH  - Cell Membrane/metabolism
MH  - Chlorides/metabolism
MH  - Convulsants/metabolism
MH  - Corticosterone/pharmacology
MH  - Flunitrazepam/metabolism
MH  - Kinetics
MH  - Male
MH  - Mammals
MH  - Neurons/*metabolism
MH  - Pregnanolone/pharmacology
MH  - Pregnenolone/pharmacology
MH  - Rats
MH  - Receptors, GABA-A/drug effects/*metabolism
MH  - Salamandridae
MH  - Species Specificity
MH  - Steroids/*pharmacology
MH  - Sulfur Radioisotopes
MH  - Synaptosomes/drug effects/*metabolism
MH  - Tritium
EDAT- 1994/05/23 00:00
MHDA- 1994/05/23 00:01
CRDT- 1994/05/23 00:00
PHST- 1994/05/23 00:00 [pubmed]
PHST- 1994/05/23 00:01 [medline]
PHST- 1994/05/23 00:00 [entrez]
AID - 0006-8993(94)90087-6 [pii]
AID - 10.1016/0006-8993(94)90087-6 [doi]
PST - ppublish
SO  - Brain Res. 1994 May 23;646(2):258-66. doi: 10.1016/0006-8993(94)90087-6.