[D-PEN(2),D-PEN(5)]ENKEPHALIN, A DELTA-OPIOID AGONIST, REDUCES ENDOGENOUS ALUMINUM CONTENT IN THE RAT CENTRAL-NERVOUS-SYSTEM

The in vivo effects of [D-Pen(2),D-Pen(5)]enkephalin, a cyclic peptide agonist with high affinity and selectivity for the delta opioid recep tors, on the endogenous aluminum content of selected areas of rat brai n and spinal cord were studied by means of atomic absorption spectroph otometry. intracerebroventricular injection of a subanalgesic dose of [D-Pen(2),D-Pen(5)]enkephalin (0.2 mu g/3 mu l) produced a transient, time-dependent reduction of the aluminum content. This effect was stat istically significant in the frontal cortex, hippocampus and striatum, but did not reach the level of significance in the medulla and thorac ic spinal cord. The partial depleting effect of [D-Pen(2),D-Pen(5)]enk ephalin on aluminum content, in the range of 0.2-1.0 mu g/3 mu l, was dose-dependent and could be reversed by naloxone pretreatment. Serum a luminum levels were unchanged after [D-Pen(2),D-Pen(5)]enkephalin trea tment. Chronic (five weeks), systemic AlCl3, treatment increased the e ndogenous aluminum content in all central nervous system areas examine d. Interestingly, [D-Pen(2),D-Pen(5)]enkephalin i.c.v. produced a slig ht 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 re ceptor binding characteristics were also studied. Neither the specific binding of [H-3][D-Pen(2),D-Pen(5)]enkephalin nor [H-3]Tyr-D-Ala-Gly- NMePhe-Gly-ol to membranes of frontal or parietal cortices, striatum o r hippocampus, prepared from rats chronically treated with AlCl3, were affected. Moreover, aluminum ions in vitro did not alter either the s pecific binding of [H-3]DPDPE or [H-3]Tyr-D-Ala-Gly-NMePhe-Gly-ol to r at cerebral membranes prepared from control animals, suggesting not on ly that chronic, systemic aluminum treatment failed to be neurotoxic t o central delta or mu opioid receptor systems in vivo, but also the ab sence of a direct receptor protein-metal ion interaction at these site s in vitro. It is concluded that [D-Pen(2),D-Pen(5)]enkephalin, and pe rhaps endogenous opioid peptides as well, via specific delta opioid re ceptors, may regulate endogenous aluminum levels or exert a modulatory action in mediating this phenomenon in the central nervous system of the rat.