Document Detail

Potent enhancement of [3H]nitrendipine binding in rat cerebral cortical and cardiac homogenates: a putative mechanism for the action of MDL 12,330A.
MedLine Citation:
PMID:  3159884     Owner:  NLM     Status:  MEDLINE    
[3H]Nitrendipine [( 3H]NTD), a specific high-affinity calcium channel antagonist, was used to label dihydropyridine binding sites associated with calcium channels in rat cerebral cortical and cardiac homogenates. A novel lactamimide compound, MDL 12,330A, has been shown previously to have negative inotropic and chronotropic effects in isolated working guinea-pig hearts and these effects are reversed by the administration of calcium. MDL 12,330A is potent in enhancing [3H]NTD binding in membranes prepared from the cerebral cortex and the heart, with EC50 values of 6.1 X 10(-8) and 3.4 X 10(-8) M, respectively, at 37 degrees C. This allosteric effect by MDL 12,330A is similar to that produced by a known calcium channel antagonist, d-cis diltiazem, which has been shown previously to enhance [3H]NTD binding at 37 degrees C. The extent of enhancement by MDL 12,330A depends on incubation temperature (37 degrees C greater than 25 degrees C greater than 0 degrees C). The mechanism of this enhancement by MDL 12,330A is due to a decrease in the dissociation rate constant of the dihydropyridine-calcium channel supramolecular complex. MDL 12,330A is the most potent drug thus far examined which demonstrates the enhancement of [3H]NTD binding.
H R Lee; J A Jaros; W R Roeske; N L Wiech; R Ursillo; H I Yamamura
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  233     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1985 Jun 
Date Detail:
Created Date:  1985-08-09     Completed Date:  1985-08-09     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  611-6     Citation Subset:  IM    
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MeSH Terms
Calcium Channel Blockers / metabolism*
Cerebral Cortex / drug effects,  metabolism*
Heart / drug effects
Imines / pharmacology*
Myocardium / metabolism*
Nifedipine / analogs & derivatives*,  metabolism
Rats, Inbred Strains
Tritium / diagnostic use
Grant Support
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Imines; 10028-17-8/Tritium; 21829-25-4/Nifedipine; 39562-70-4/Nitrendipine; 82985-31-7/RMI 12330A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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