High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

Kevin P Campbell; Alan Sharp; Molly Strom; Steven D Kahl

doi:10.1073/pnas.83.9.2792

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High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

Journal article

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High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers

Kevin P Campbell, Alan Sharp, Molly Strom and Steven D Kahl

Proceedings of the National Academy of Sciences - PNAS, Vol.83(9), pp.2792-2796

1986

DOI: 10.1073/pnas.83.9.2792

PMCID: PMC323392

PMID: 3010317

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Abstract

Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind [3H]nitrendipine, [3H]-nimodipine, [3H]nisoldipine, and [3H]PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while [3H]verapamil, [3H]diltiazem, and [3H]trifluoperazine were not recognized. The average dissociation constant of the [3H]nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of [3H]nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify [3H]nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace [3H]nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers.

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Details

Title: Subtitle: High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers
Creators: Kevin P Campbell - Univ. Iowa, dep. physiology biophysics
Alan Sharp - Univ. Iowa, dep. physiology biophysics
Molly Strom - Univ. Iowa, dep. physiology biophysics
Steven D Kahl - Univ. Iowa, dep. physiology biophysics
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.83(9), pp.2792-2796
DOI: 10.1073/pnas.83.9.2792
PMID: 3010317
PMCID: PMC323392
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences; Washington, DC
Language: English
Date published: 1986
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984068265202771

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