Inhibition of (/sup 3/H)nitrendipine binding by phospholipase A/sub 2/
Phospholipase A/sub 2/ from several sources inhibited (/sup 3/H)nitrendipine binding to membranes from brain, heart and ileal longitudinal muscle. The enzymes from bee venom and Russell's viper venom were most potent, having IC/sub 50/ values of approximately 5 and 14 ng/ml, respectively, in all three membrane preparations. Inhibition of binding by bee venom phospholipase A/sub 2/ was time- and dose-dependent. Mastoparan, a known facilitator of phospholipase A/sub 2/ enzymatic activity, shifted the bee venom phospholipase A/sub 2/ dose-response curve to the left. Pretreatment of brain membranes with bee venom phospholipase A/sub 2/ (10 ng/ml) for 15 min caused a 2-fold increase in the K/sub d/ without changing the B/sub max/ compared with untreated membranes. Extension of the preincubation period to 30 min caused no further increase in the K/sub d/ but significantly decreased the B/sub max/ to 71% the value for untreated membranes. (/sup 3/H)Nitrendipine, preincubated with bee venom phospholipase A/sub 2/, was recovered and found to be fully active, indicating that the phospholipase A/sub 2/ did not modify the ligand. It is concluded that phospholipase A/sub 2/ acts on the membrane at or near the (/sup 3/H)nitrendipine binding site and that phospholipids play a key role in the interactions of 1,4 dihydropyridine calcium channel antagonists with the dihydropyridine binding site. 33 references, 3 figures, 1 table.
- Research Organization:
- NIH, Bethseda, MD
- OSTI ID:
- 5254508
- Journal Information:
- Life Sci.; (United States), Vol. 37:14
- Country of Publication:
- United States
- Language:
- English
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LIPASE
ENZYME ACTIVITY
PYRIDINES
CHEMICAL BONDS
BRAIN
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DOSE-RESPONSE RELATIONSHIPS
HEART
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MUSCLES
TIME DEPENDENCE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VENOMS
AZINES
BODY
CARBOXYLESTERASES
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
ENZYMES
ESTERASES
HETEROCYCLIC COMPOUNDS
HYDROLASES
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ORGANIC NITROGEN COMPOUNDS
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550201* - Biochemistry- Tracer Techniques