PMID- 2578767
OWN - NLM
STAT- MEDLINE
DCOM- 19850321
LR  - 20190628
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 237
IP  - 1
DP  - 1985 Feb 15
TI  - Induction of methotrexate release from rat hepatocytes in suspension by 
      alpha-adrenergic agents: involvement of calcium and metabolic energy.
PG  - 237-43
AB  - Hepatocytes in suspension which have accumulated [3H]methotrexate release the 
      antifolate compound into the medium upon exposure to alpha-adrenergic agents. In 
      the presence of metabolic poisons, such as sodium azide, dinitrophenol, or 
      dicumarol, the release of methotrexate is attenuated, indicating that integrity 
      of the cellular metabolic apparatus is required for response to the hormonal 
      stimulus. In the presence of millimolar concentrations of the organic acid, 
      probenecid, release of cellular methotrexate may be reduced (1 mM probenecid) or 
      eliminated (2 mM probenecid), suggesting the involvement of a "membrane carrier." 
      Microtubule poisons such as vincristine, vinblastine, and griseofulvin do not 
      modify epinephrine + isobutyl methyl xanthine (IBMX)-induced release of 
      methotrexate. The involvement of calcium in release of methotrexate from the 
      hepatocyte is substantiated by a dose-dependent response to the calcium 
      ionophore, A23187, in the presence of calcium, with a lack of response in the 
      absence of calcium. These effects of A23187 are not related to inhibition of 
      methotrexate influx. Other putative "calcium antagonists" such as tetracaine, 
      neomycin sulfate, and 3,4,5-trimethoxybenzoic acid [8-(diethylamino)octyl ester], 
      do not interfere with epinephrine + IBMX-induced release of [3H]methotrexate, 
      suggesting that these agents may not be effective probes of calcium flux in the 
      liver cell.
FAU - Gewirtz, D A
AU  - Gewirtz DA
FAU - Randolph, J K
AU  - Randolph JK
FAU - Jaramillo, M
AU  - Jaramillo M
LA  - eng
GR  - AM18476/AM/NIADDK NIH HHS/United States
GR  - CA16906/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Adrenergic alpha-Agonists)
RN  - 25513-46-6 (Polyglutamic Acid)
RN  - 37H9VM9WZL (Calcimycin)
RN  - 82334-40-5 (methotrexate polyglutamate)
RN  - SY7Q814VUP (Calcium)
RN  - TBT296U68M (1-Methyl-3-isobutylxanthine)
RN  - YKH834O4BH (Epinephrine)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - 1-Methyl-3-isobutylxanthine/pharmacology
MH  - Adrenergic alpha-Agonists/*pharmacology
MH  - Animals
MH  - Biological Transport, Active/drug effects
MH  - Calcimycin/pharmacology
MH  - Calcium/*physiology
MH  - Energy Metabolism/*drug effects
MH  - Epinephrine/pharmacology
MH  - In Vitro Techniques
MH  - Liver/drug effects/*metabolism
MH  - Male
MH  - Methotrexate/analogs & derivatives/*metabolism
MH  - Polyglutamic Acid/analogs & derivatives/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
EDAT- 1985/02/15 00:00
MHDA- 1985/02/15 00:01
CRDT- 1985/02/15 00:00
PHST- 1985/02/15 00:00 [pubmed]
PHST- 1985/02/15 00:01 [medline]
PHST- 1985/02/15 00:00 [entrez]
AID - 0003-9861(85)90274-7 [pii]
AID - 10.1016/0003-9861(85)90274-7 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1985 Feb 15;237(1):237-43. doi: 
      10.1016/0003-9861(85)90274-7.