PMID- 9106255
OWN - NLM
STAT- MEDLINE
DCOM- 19970724
LR  - 20190831
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 30
IP  - 4-5
DP  - 1997 Apr-May
TI  - Effects of nerve growth factor on dihydrotetrabenazine binding to PC12 cells.
PG  - 411-5
AB  - Tetrabenazine and dihydrotetrabenzaine (TBZOH) are potent inhibitors of substrate 
      transport by the predominant forms of the vesicular monoamine transporter (VMAT) 
      present in bovine brain synaptic vesicles and bovine adrenal medullary chromaffin 
      vesicles. Radiolabeled TBZOH binds to these preparations with apparent 
      dissociation constants in the low nanomolar range. However, tetrabenazine is a 
      much less potent inhibitor of transport by rVMAT1, a form of the transporter 
      cloned from a rat pheochromocytoma (PC12) cDNA library and expressed in CHO 
      cells. Reported attempts to observe binding of [3H]TBZOH to rVMAT1 have not been 
      successful. We examined binding of [3H]TBZOH to a crude membrane fraction from 
      PC12 cells. Computerized nonlinear least squares curve fitting revealed two 
      classes of binding sites (Kd1 = 1.5 nM, R1 = 0.2 pmol/mg protein, Kd2 = 340 nM, 
      R2 = 15.2 pmol/mg protein). While the identity of the higher affinity sites is 
      not certain, their high affinity for TBZOH suggests that they may be associated 
      with rVMAT2. The lower affinity sites are likely to be associated with rVMAT1 on 
      the basis of their affinity for TBZOH and sensitivity to inhibition of TBZOH 
      binding by transporter substrates and inhibitors. NGF-treated PC12 cells also 
      exhibited two classes of sites (Kd1 = 1.9 nM, R1 = 0.18 pmol/mg protein; Kd2 = 
      370 nM, R2 = 23.7 pmol/mg protein). While there were no significant differences 
      between control and NGF-treated cells in binding capacity of the higher affinity 
      sites, nor in apparent dissociation constants for either class of sites, there 
      was a highly significant increase in number of lower affinity binding sites in 
      the NGF-treated cells (p = 0.001). These results provide direct evidence that the 
      differential sensitivity of rat brain and adrenal catecholamine stores to 
      depletion by tetrabenazine and its derivatives is due to a much lower affinity of 
      rVMAT1 for these compounds, and that NGF treatment may increase levels of rVMAT1 
      expression in PC12 cells.
FAU - Adamson, C R
AU  - Adamson CR
AD  - Medical Sciences Program, Indiana University School of Medicine, Bloomington 
      47405, USA.
FAU - Emley, T E
AU  - Emley TE
FAU - Herbig, L J
AU  - Herbig LJ
FAU - Near, J A
AU  - Near JA
LA  - eng
GR  - NS20784/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Neuropeptides)
RN  - 0 (Neurotransmitter Agents)
RN  - 0 (Vesicular Biogenic Amine Transport Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 3466-75-9 (dihydrotetrabenazine)
RN  - Z9O08YRN8O (Tetrabenazine)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Biological Transport/drug effects
MH  - Cattle
MH  - Kinetics
MH  - Membrane Glycoproteins/metabolism
MH  - *Membrane Transport Proteins
MH  - Nerve Growth Factors/*pharmacology
MH  - *Neuropeptides
MH  - Neurotransmitter Agents/metabolism
MH  - PC12 Cells
MH  - Rats
MH  - Tetrabenazine/*analogs & derivatives/metabolism
MH  - Vesicular Biogenic Amine Transport Proteins
MH  - Vesicular Monoamine Transport Proteins
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
AID - 10.1016/s0197-0186(96)00076-9 [doi]
PST - ppublish
SO  - Neurochem Int. 1997 Apr-May;30(4-5):411-5. doi: 10.1016/s0197-0186(96)00076-9.