Opioid peptides modulate neurotransmitter release and myocardial contraction. However, the cellular mechanisms underlying their effects are not known. In particular, their effects on cytosolic Ca 2+ (Cai) homeostasis are still largely undefined. The present study shows that in rat ventricular myocytes loaded with the Ca 2+ probe indo-1, the k opioid receptor agonist (trans-,(dl)-3, 4-dichloro-N-methyl-N- [2-(l-pyrrolidinyl) cyclo-hexyl] -benzeneacetamide) methane sulfonate hydrate (U-50,488H) causes a transient increase followed by a monotonic decrease in the amplitude of the twitch and of the Cai transient, indexed as the 410/490 nm ratio of indo-1 fluorescence. Under similar conditions the delta- opioid leucine-enkephalin decreases twitch and Cai amplitudes without causing a transient increase in either signal. In the absence of electrical stimulation U-50,488H and leucine-enkephalin slowly increase Cai or cause Cai oscillations and eventually abolish the caffeine-triggered Cai transient. This occurs in both myocytes and, neuroblastoma-2a cells. These effects of the U-50,488H and leucine enkephalin on both cell types are prevented by the k and delta opioid receptor blockers (-)-N-(3-Furylmethyl)- a-normetazocinel methansulphonate (Mr 1452) and naloxone. In cardiac myocyte suspensions U-50,488H and leucine-enkephalin both cause a rapid and sustained increase in inositol-1,4,5-trisphosphate (IP3). The peak effect of the k agonist on IP3 production is of greater magnitude and occurs with a faster time course than that of the delta opioid and may account for the different effects of these peptides on the Cai transient in electrically stimulated cardiac myocytes. Thus, both in cardiac cells and neurons k and delta opioid receptors appear to be coupled to phosphatidylinositol turnover leading to Ca 2+ release from intracellular stores.
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