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Interactions of Divalent Cations and Guanine Nucleotides at α 2 ‐Noradrenergic Receptor Binding Sites in Bovine Brain Mechanisms
Author(s) -
U'Prichard David C.,
Snyder Solomon H.
Publication year - 1980
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1980.tb06608.x
Subject(s) - gtp' , divalent , chemistry , agonist , guanine , binding site , g protein , nucleotide , sodium , magnesium , biophysics , membrane , receptor , biochemistry , biology , enzyme , organic chemistry , gene
Guanine nucleotides selectively decrease binding of the agonist ligands [ 3 H]clonidine and [ 3 H]epinephrine to α 2 ‐noradrenergic receptors in calf cortex membranes. In the presence of 1.0 mM‐calcium,‐magnesium, ormanganese, inhibition by GTP of [ 3 H]clonidine binding is reversed, so that low concentrations of GTP increase [ 3 H]clonidine binding, whereas high GTP concentrations cause a secondary decrease. In the presence of divalent cations, low concentrations of guanyl‐5′‐yl imidodiphosphate [Gpp(NH)p], unlike GTP, do not increase binding. Differences between effects of GTP and Gpp(NH)p in the presence of divalent cations are also observed with [ 3 H]epinephrine binding to rat and calf cortex α 2 ‐receptors. In reversing the inhibition of α 2 ‐agonist binding by GTP, manganese, with an ED 50 of 21 μM, is much more potent and effective than magnesium or calcium. Manganese by itself increases [ 3 H]clonidine binding by 20% an effect which is irreversible, while the interactive effects of manganese and GTP are reversible. Divalent cations also antagonize the sodium‐induced inhibition of α 2 ‐agonist binding in calf cortex membranes, and manganese has similar ED 50 values in antagonizing both sodium and GTP.