The effect of opiate agonists and antagonists on Na+-Ca2+ exchange in cardiac sarcolemma vesicles

Daniel Khananshvili*, Yosef Sarne

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Opiate agonists and antagonists inhibit Na+-Ca2+ exchange in the isolated cardiac sarcolemma vesicles. Non-opioid stereoisomers (dextrorphan, Mr 1542MS, WIN 44,441-3) display effects similar to their opioid isomers (levorphanol, Mr 1543MS, WIN 44,441-2) suggesting that inhibition is not mediated by opiate receptors. Naloxone (permeable) and methylnaloxone (impermeable) inhibit the Na+-Ca2+ exchange similarly, suggesting an extravesicular location of inhibitory site. The inhibitory potency of naloxone is pH-independent in the range of 7.4-9.1, suggesting that the charge-carrying properties of drug-protein interactions are not altered under the tested conditions. Opiates display similar dose-response relationships for Na+-Ca2+ exchange and its partial reaction, the Ca2+-Ca2+ exchange. The opiate-induced inhibition is complete and noncompetitive in regard to extravesicular calcium. These data suggest that opiates do not bind to the Ca2+-binding domain (A-site), but they may interact either with the Na+-binding site (B-site) or with a putative opiate-binding site, presumably located outside of the ion-binding vicinity. Further studies on structure-activity relationship might lead to the discovery of potent and more specific inhibitors of cardiac Na+-Ca2+ exchanger. A possible relevance of these findings to some non-opioid pharmacological effects of naloxone on the cardiac muscle is suggested.

Original languageEnglish
Pages (from-to)275-283
Number of pages9
JournalLife Sciences
Issue number4
StatePublished - 1992


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