The in vivo effects of [d-Pen2,d-Pen5]enkephalin, a cyclic peptide agonist with high affinity and selectivity for the δ opioid receptors, on the endogenous aluminum content of selected areas of rat brain and spinal cord were studied by means of atomic absorption spectrophotometry. Intracerebroventricular injection of a subanalgesic dose of [d-Pen2,d-Pen5]enkephalin (0.2 μg/3 μl) produced a transient, time-dependent reduction of the aluminum content. This effect was statistically significant in the frontal cortex, hippocampus and striatum, but did not reach level of significance in the medulla and thoracic spinal cord. The partial depleting effect of [d-Pen2,d-Pen5]enkephalin on aluminum content, in the range of 0.2-1.0 μg/3 μl, was dose-dependent and could be reversed by naloxone pretreatment. Serum aluminum levels were unchanged after [d-Pen2,d-Pen5]enkephalin treatment. Chronic (five weeks), systemic AlCl3 treatment increased the endogenous aluminum content in all central nervous system areas examined. Interestingly, [d-Pen2,d-Pen5]enkephalin i.c.v. produced a slight depletion of this elevated metal level in these areas to values not significantly different from those of the respective control values. Chronic in vivo, as well as in vitro, effects of aluminum on opioid receptor binding characteristics were also studied. Neither the specific binding of [3H][d-Pen2,d-Pen5]enkephalin nor [3H]Tyr-d-Ala-Gly-NMePhe-Gly-ol to membranes of frontal or parietal cortices, striatum or hippocampus, prepared from rats chronically treated with AlCl3, were affected. Moreover, aluminum ions in vitro did not alter either the specific binding of [3H]DPDPE or [3H]Tyr-d-Ala-Gly-NMePhe-Gly-ol to rat cerebral membranes prepared from control animals, suggesting not only that chronic, systemic aluminum treatment failed to be neurotoxic to central δ or μ opioid receptor systems in vivo, but also the absence of a direct receptor protein-metal ion interaction at these sites in vitro. It is concluded that [d-Pen2,d-Pen5]enkephalin, and perhaps endogenous opioid peptides as well, via specific δ opioid receptors, may regulate endogenous aluminum levels or exert a modulatory action in mediating this phenomenon in the central nervous system of the rat.
- Alzheimer's disease
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