Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/12826
Title: The effect of hypoxia and of energy depletion on 1,4-dihydropyridine binding sites in rat cardiac membrane fragments.
Authors: Gu, X H;Dillon, J S;Nayler, W G
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Issue Date: 15-Jun-1989
Citation: Biochemical Pharmacology; 38(12): 1897-907
Abstract: The effect of hypoxia, reoxygenation and chemically-induced high energy phosphate depletion (caused by inhibition of oxidative phosphorylation and glycolysis) on the affinity (Kd), density (Bmax) and selectivity of high affinity 1,4-dihydropyridine (DHP) calcium antagonist binding sites was studied in rat isolated cardiac membranes, using (+)[3H]PN200-110. Neither 30 nor 60 min normothermic (37 degrees) hypoxia affected either the Bmax or Kd of these sites, relative to aerobic controls. Fifteen min reoxygenation after 60, but not 30, min hypoxia reduced the density of the DHP binding sites, without altering their affinity or selectivity. Aerobic perfusion with 0.1 mM DNP (an uncoupler of oxidative phosphorylation) for 30 min at 37 degrees caused an increase in Bmax (P less than 0.05) both in the presence (48%) and absence (27%) of glucose, without any change in Kd. This increase in Bmax was attenuated during a further 30 min perfusion with DNP. Thirty min perfusion with 1.0 mM IAA and 0.1 mM DNP resulted in a significant increase (27%) in the Bmax of the DHP binding sites. A further 30 min perfusion with IAA and DNP caused the Bmax to return to control levels. The Kd was not altered under these conditions. Irrespective of the perfusion conditions, the selectivity of the binding sites was unchanged, with (+)PN200-100 greater than (-)Bay K8644 greater than (-)PN200-110 = (+)Bay K8644 in displacing bound (+)[3H]PN200-110. Under all conditions, (-)D600 always interacted allosterically with the DHP binding sites, and the binding was stimulated by d-cis diltiazem. These results show that neither hypoxia nor chemically-induced ATP depletion mimic the effect of ischaemia on cardiac DHP binding sites.
Internal ID Number: 2742598
URI: http://ahro.austin.org.au/austinjspui/handle/1/12826
URL: http://www.ncbi.nlm.nih.gov/pubmed/2742598
Type: Journal Article
Subjects: 2,4-Dinitrophenol
Allosteric Site
Animals
Dihydropyridines.metabolism
Dinitrophenols.pharmacology
Energy Metabolism
In Vitro Techniques
Male
Myocardium.metabolism
Oxidative Phosphorylation
Oxygen.metabolism
Perfusion
Phosphates.metabolism
Rats
Rats, Inbred Strains
Uncoupling Agents
Appears in Collections:Journal articles

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