Regulation of endogenous calcium and magnesium levels by delta opioid receptors in the rat brain.

The effects of the potent agonist (D-Pen2, D-Pen5) enkephalin (DPDPE), a conformationally restricted ligand which is highly selective for delta opioid receptors, were studied on the endogenous levels and regional distributions of selected mono- and divalent cations in rat brain and thoracic spinal cord by means of atomic absorption spectrophotometry. In general, lower Na+, K+, Ca2+, Mg2+ and Mn2+ levels were characteristic of the medulla and spinal cord compared to that of cortices, striatum and hippocampus, while the highest metal ion levels were detected in the olfactory bulb. Sixty minutes after a single dose of 0.2 microgram DPDPE, administered intracerebroventricularly, transient decreases of endogenous Ca2+ and Mg2+ contents in the parietal cortex, hippocampus and striatum were found with no changes observed in the levels of monovalent cations or Mn2+. A time-dependent down-regulation in Ca2+ and Mg2+ content was also demonstrated, with Ca2+ being faster to respond to DPDPE treatment. The action of DPDPE was dose-dependent (0.2-1.0 micrograms) and could be antagonized by a 30 min naloxone pretreatment. Naloxone alone had no effect on the endogenous cation levels. It is concluded that delta opioid receptors may specifically be involved in the regulation of endogenous ion levels and their movements in the central nervous system of rat.