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Guanine Nucleotide and Cation Regulation of μ, δ, and k Opioid Receptor Binding: Evidence for Differential Postnatal Development in Rat Brain

Authors


  • Dr. M. Szücs is on leave from Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.

Address correspondence and reprint requests to Dr. C. J. Coscia at E. A. Doisy Department of Biochemistry, St. Louis University School of Medicine, St. Louis, MO 63 104, U.S.A.

Abstract

Abstract: A study of the onset of cation and guanine nucleotide regulation of δ, μ, and k rat brain opioid receptors during postnatal development was undertaken. Site-specific binding assays were utilized for each receptor type and the effects of 0.5 mM MnCl2, 100 mM NaCl, and/or 50 μM guanosine-5′-(β,γ-imido) triphosphate [GPP(NH)P] were assessed. The most pronounced changes of opioid binding were seen in the presence of Mn2+. In adults, agonist binding to δ sites was stimulated by Mn2+, whereas that to μ. sites was not affected and k binding was inhibited. The postnatal development of Mn2+ regulation for the three receptor subtypes was distinctly different. The largest effects were seen on δ sites detected in the early neonatal period, Mn2+ eliciting a 68% stimulation of binding over controls at day 1. Significant inhibition of k site binding by Mn2+ was detected only after the third postnatal week. Mn2+ caused a significant reversal of Gpp(NH)p inhibition of δ binding in the early neonatal period, exceeding that in the absence of regulators. Inhibition of μ and δ receptor binding by Na+ was greater, and the Mn2+ reversal of this effect was smaller, in the first 2 postnatal weeks than in adults. Gpp(NH)p + Na+ regulation did not change appreciably during the postnatal period. However, Mn2+ reversal of the considerable inhibition elicited by the combination of Na+ and Gpp(HN)p was developmental time-dependent. The data are discussed in terms of multiple sites of interaction for guanine nucleotides and cations. Our results demonstrate that the characteristics and postnatal development of guanine nucleotide and cat-ionic regulation of μ, δ, and k binding are distinctly different. Furthermore, neonates may serve as a model for the examination of individual regulatory effects on opioid receptors.

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