Leucine-enkephalin increases the level of inositol (1,4,5) triphosphate and releases calcium from an intracellular pool in rat ventricular cardiac myocytes.

In rat ventricular cardiomyocytes loaded with the fluorescent Ca2+ indicator Indo-1/AM, the delta opioid receptor agonist Leu-Enk caused Cai oscillations and abolished the caffeine-induced Cai transient. During superfusion of cardiomyocytes with the specific opioid antagonist naloxone, Cai is not affected by Leu-Enk and the caffeine-triggered Cai transient is preserved. In parallel experiments with cardiac myocytes, the delta opioid agonist increased the intracellular level of Ins (1,4,5) P3 by about 4 times above the control value. Such an effect was completely antagonized by naloxone. Thus, Leu-Enk induces depletion of Ca2+ from the SR by a receptor-mediated mechanism which appears to involve an increase in the intracellular level of Ins (1,4,5) P3.