Distinct components of morphine effects on cardiac myocytes are mediated by the κ and δ opioid receptors

Catherine Ela, Jacob Barg, Zvi Vogel, Yonathan Hasin, Yael Eilam

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Morphine exerts direct effects on cultured cardiac myocytes from neonatal rats. These effects are mediated via the δ and the κ opioid receptors, as μ opioid receptors are not present in neonatal cardiomyocyte cultures. Binding parameters to the δ and κ opioid receptors were determined in membrane preparations from these cultures by heterologous competition to [3H]diprenorphine binding, with [D-Pen2, D-Pen5]-enkephalin (DPDPE) and trans-(dl)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] -benzeneacetamide methanesulfonate (U-50,488H) as specific displacers respectively. To define the components of morphine effects mediated via activation of either the δ or the κ opioid receptor alone, cardiac myocytes were exposed to morphine in the presence of specific antagonists to the κ or δ opioid receptor respectively. Activation of the κ opioid receptors by morphine caused a transient increase in Ca2+ influx, leading to increase in amplitudes of [Ca2+](i) transients and contraction, with no change in the intracellular pH. Activation of the δ opioid receptors alone by morphine caused a decrease in the amplitude of contraction. This decrease was mediated by a decrease in the intracellular pH leading to reduced responsiveness of the myofilaments to Ca2+. There was no change in Ca2+ influx and in the amplitude of [Ca2+] transients. The effects mediated through the δ opioid but not through the κ opioid receptors were pertussis toxin sensitive, indicating coupling of the δ opioid receptors to pertussis toxin sensitive GTP-binding proteins. The overall effects of morphine on the neonatal cardiac myocytes were the sum of the effects exerted by morphine when it activated each of the opioid receptors alone.

Original languageEnglish
Pages (from-to)711-720
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Issue number2
StatePublished - Feb 1997
Externally publishedYes


  • Cardiac myocytes
  • Contractility
  • Cystolic Ca
  • Intracellular pH
  • Morphine
  • Opioid receptors


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