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Regulation of ligand binding to leukotriene D4 receptors: effects of cations and guanine nucleotides

, : Regulation of ligand binding to leukotriene D4 receptors: effects of cations and guanine nucleotides. European Journal of Pharmacology 106(2): 241-253

High affinity, stereoselective specific binding sites for [3H]leukotriene D4 [( 3H]LTD4) have been demonstrated in guinea pig lung membranes. Purine nucleotides quantitatively reduced [3H]LTD4 specific binding with a rank order potency of guanosine-5'-O-3-thiotriphosphate (GTP gamma S) = guanyl-5'-yl-imido-diphosphate [Gpp(NH)p] greater than GTP greater than ATP greater than GDP. In the presence of 1 microM Gpp(NH)p, the maximum number (Bmax) of [3H]LTD4 specific binding sites was reduced to 41 +/- 10 percent of the control level (950 +/- 150 fmol/mg membrane protein). In the presence of 3 microM Gpp(NH)p, the rate of association of [3H]LTD4 to the specific sites was estimated to have increased 2.5-fold. The rate of dissociation of [3H]LTD4 from the specific sites was also increased significantly in the presence of 50 microM Gpp(NH)p. The divalent cations, Ca2+ and Mg2+ (10 mM), increased the Bmax 2-fold and had minimal effects on the dissociation constant (Kd) of [3H]LTD4 specific binding. Sodium ions, at a concentration of 50 mM, reduced the Bmax, and had minimal effects on the Kd of [3H]LTD4 specific binding. These data indicate that guanine nucleotides, Na+, Mg2+ and Ca2+ regulate [3H]LTD4 binding to its receptors in guinea pig lung.

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Accession: 044174724

PMID: 6099273

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