The agonist-specific effect of magnesium ion on binding by beta-adrenergic receptors in S49 lymphoma cells. Interaction of GTP and magnesium in adenylate cyclase activation.

Bird, Susan J.; Maguire, Michael E.

doi:10.1016/s0021-9258(17)34252-7

Cited by 105 publications

(7 citation statements)

References 39 publications

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“…Rodbell et al (1971a,b) demonstrated that EDTA promotes dissociation of 125I-glucagon from rat liver plasma membranes and that GTP decreases the level of steady-state binding in the presence, but not the absence, of EDTA. Also, Mg2+ binds to and facilitates activation of Ns (Iyengar, 1981;Iyengar & Birnbaumer, 1981;Sternweis et al, 1981) and increases 0-adrenergic agonist binding to membranes from a variety of cells (Williams et al, 1978;Bird & Maguire, 1978;Heidenreich et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

“…Factors such as guanine nucleotides and Mg2+ that affect the conformation of Ns (Sternweis et al, 1981; Godina et al, 1984) affect receptor-regulatory protein interactions and ligand-receptor binding. For example, Mg2+ increases ^-adrenergic agonist binding by increasing receptor affinity for ligand (Williams et al, 1978;Bird & Maguire, 1978). GTP promotes disaggregation of receptor-N protein complexes (Rodbell, 1980) and thereby increases the dissociation of 125I-glucagon from rat liver plasma membranes…”

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confidence: 99%

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Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns

Lipson¹,

Maki²,

Donner³

1988

Biochemistry

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The effects of Mg2+ or ethylenediaminetetraacetic acid (EDTA) on 125I-glucagon binding to rat liver plasma membranes have been characterized. In the absence of guanosine 5'-triphosphate (GTP), maximal binding of 125I-glucagon occurs in the absence of added Mg2+. Addition of EDTA or Mg2+ diminishes binding in a dose-dependent manner. In the presence of GTP, maximal binding occurs in the presence of 2.5 mM Mg2+ (EC50 = 0.3 mM) while EDTA or higher concentrations of Mg2+ diminish binding. Response to exogenous Mg2+ or EDTA depends on the concentration of Mg2+ in the membranes and may vary with the method used for membrane isolation. Solubilized 125I-glucagon-receptor complexes fractionate on gel filtration columns as high molecular weight, GTP-sensitive complexes in which receptors are coupled to regulatory proteins and lower molecular weight, GTP-insensitive complexes in which receptors are not coupled to other components of the adenylyl cyclase system. In the absence of GTP, 40 mM Mg2+ or 5 mM EDTA diminishes receptor affinity for hormone (from KD = 1.2 +/- 0.1 nM to KD = 2.6 +/- 0.3 nM) and the fraction of 125I-glucagon in high molecular weight receptor-Ns complexes without affecting site number (Bmax = 1.8 +/- 0.1 pmol/mg of protein). Thus, while GTP promotes disaggregation of receptor-Ns complexes, Mg2+ or EDTA diminishes the affinity with which these species bind hormone. In the presence of GTP, hormone binds to lower affinity (KD = 9.0 +/- 3.0 nM), low molecular weight receptors uncoupled from Ns.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns

Lipson¹,

Maki²,

Donner³

1988

Biochemistry

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“…The failure of magnesium to increase the apparent affinity is difficult to reconcile with the ternary model if one assumes that the cation acts to decrease the value of KG, thereby favoring the association of R and G. The absence of an effect is particularly noteworthy in view of the relatively large increase in capacity (approximately 85%, Heidenreich et al, 1982; 40-90%, Hulme et al, 1983). If [G]t equals [R], and the agonist favors RG over free R, a decrease in KG is expected to have little or no effect on A", (eq 5) only when most of the receptors are in the coupled state in the absence of magnesium (Figure 4); in contrast, both /3-adrenergic and muscarinic receptors appear to be predominantly in a state of lower affinity in the absence of magnesium (Bird & Maguire, 1978;Cech et al, 1980;Hulme et al, 1983).…”

Section: Discussionmentioning

confidence: 99%

Assessment of ternary model for the binding of agonists to neurohumoral receptors

Lee¹,

Sole²,

Wells³

1986

Biochemistry

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A frequently cited variant of the "mobile receptor" hypothesis has been examined for its ability to describe the binding of agonists at neurohumoral receptors that operate via a guanylyl nucleotide binding protein. The model involves a reversible association between the receptor (R) and the G protein (G). Agonists (A) bind with different affinity to R and to the RG complex; similarly, G differentiates between R and the AR complex. Theoretical binding curves calculated according to the model have been analyzed in terms of the Hill equation and as a mixture of independent and noninteracting sites. The model is shown to be compatible in some respects with reported data on the binding of agonists to the beta-adrenergic receptor but not to the muscarinic cholinergic or D2 dopaminergic receptors. It is difficult to reconcile with the reported effects of guanylyl nucleotides, magnesium, and N-ethylmaleimide on the binding of agonists at any neurohumoral receptor.

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“…Magnesium cations have a profound stimulatory effect on the interaction of many G protein coupled receptors with their agonists. The list of receptors that fall into this category includes β-adrenergic receptor (β-AR) (Bird andMaguire 1978, Williams et al 1978), α2-adrenergic receptor (α2-AR) (Tsai and Lefkowitz 1978, Glossmann and Presek 1979, muscarinic acetylcholine receptor (mACh-R) (Wei andSulakhe 1980, Hilf et al 1989) and receptors for PGE1 (prostaglandin E 1 ) (Williams et al 1978), opioids , dopamine (Sibley and Creese 1983) and chemotactic formyl peptide receptors (Gierschik et al 1989(Gierschik et al , 1991. In most cases, the major effect of magnesium cations was an increase in receptor affinity for the agonist [β-AR (Bird andMaguire 1978, Williams et al 1978) and α2-AR (Tsai and Lefkowitz 1978)], although an increase in the number of binding sites was also noticed [mACh-R (Glossmann and Presek 1979)].…”

Section: Lithium Magnesium and Trimeric G Proteinsmentioning

confidence: 99%

“…Therefore, the effect of magnesium cations is diametrically opposite to the effect of guanine nucleotides, which are well known to reduce agonist affinity of all GPCRs. As the latter effect is due to a nucleotide-dependent functional and physical uncoupling of the receptor from G protein, it has been suggested that magnesium cations enhance agonist binding by stabilization of ternary, highaffinity complex H-R-G (complex hormone-receptor-G protein) which is necessary intermediate for hormonal stimulation of effector enzymes as well as guanine nucleotide-dependent transition of receptor from the high to low-affinity state (Bird and Maguire 1978, Tsai and Lefkowitz 1978, Williams et al 1978. It was suggested that lithium interaction with G proteins may proceed as direct competition with magnesium ions bound to the low-affinity Mg2+-sites in Gα subunits (Malarkey et al 2008).…”

Section: Lithium Magnesium and Trimeric G Proteinsmentioning

confidence: 99%

Lithium – therapeutic tool endowed with multiple beneficiary effects caused by multiple mechanisms

Vošahlíková¹,

Svoboda²

2016

Acta Neurobiologiae Experimentalis

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Mood disorders are relatively common serious human diseases for which there is often no ideal pharmacotherapy. Basic characteristic of these diseases is affective disorder shifting the mood of the patient to depression (together with anxiety or not) or towards to euphoria. Available drugs are usually divided into two groups -mood stabilizers, which are used primarily to treat bipolar disorder, and antidepressants for the treatment of unipolar depression. Lithium is still recommended as the first choice for dealing with bipolar disorder. Despite abundant clinical use of mood stabilizing drugs, important questions regarding their mechanism of action remain open.In this paper we present the brief review of rather diversified hypotheses and ideas about mechanisms of genesis of mood disorders and lithium interferences with these pathological states. New data derived from the high-resolution crystallographic studies of allosteric,

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The agonist-specific effect of magnesium ion on binding by beta-adrenergic receptors in S49 lymphoma cells. Interaction of GTP and magnesium in adenylate cyclase activation.

Cited by 105 publications

References 39 publications

Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns

Divalent cations regulate glucagon binding. Evidence for actions on receptor-Ns complexes and on receptors uncoupled from Ns

Assessment of ternary model for the binding of agonists to neurohumoral receptors

Lithium – therapeutic tool endowed with multiple beneficiary effects caused by multiple mechanisms

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