Transition of affinity states for leukotriene B4 receptors in sheep lung membranes

Votta, Bartholomew J.; Mong, Seymour

doi:10.1042/bj2650841

Cited by 16 publications

(5 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During a brief, initial exposure to LTB 4 , PMNs are recruited [85], whereas prolonged exposure elicits additional responses including superoxide anion radical formation and degranulation [86,87]. LTB 4 activity is mediated by BLT receptors, whose cloning has revealed interspecies differences [88,89]. Two subclasses of BLT receptors have been identified, BLT-1 and BLT-2, both members of the G-protein-coupled receptor (GPCR) family [88].…”

Section: 1a Leukotriene-b 4 Receptorsmentioning

confidence: 99%

“…LTB 4 activity is mediated by BLT receptors, whose cloning has revealed interspecies differences [88,89]. Two subclasses of BLT receptors have been identified, BLT-1 and BLT-2, both members of the G-protein-coupled receptor (GPCR) family [88]. BLT-2 is a ubiquitous, lowaffinity receptor with notable presence in liver, intestine, spleen, and kidney, whereas BLT-1 is found predominantly in PMNs [90], and has been detected in human carotid artery atherosclerotic plaques, endothelial cells, and smooth muscle cells [91].…”

Section: 1a Leukotriene-b 4 Receptorsmentioning

confidence: 99%

See 1 more Smart Citation

Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers

Khanapure¹,

Garvey²,

Janero³

et al. 2007

CTMC

284

188

View full text Add to dashboard Cite

In mammalian cells, eicosanoid biosynthesis is usually initiated by the activation of phospholipase A2 and the release of arachidonic acid (AA) from membrane phospholipids. The AA is subsequently transformed by cyclooxygenase (COX) and lipoxygenase (LO) pathways to prostaglandins, thromboxane and leukotrienes collectively termed eicosanoids. Eicosanoid production is considerably increased during inflammation. Both COX and LO pathways are of particular clinical relevance. The COX pathway is the major target for non-steroidal anti-inflammatory drugs (NSAIDs), the most popular medications used to treat pain, fever and inflammation. Although their anti-inflammatory effects are well known, their long-term use is associated with gastrointestinal (GI) complications such as ulceration. In 1991, it was discovered that COX exists in two distinct isozymes, COX-1 and COX-2, of which COX-2 is primarily expressed at sites of inflammation and produces pro-inflammatory eicosanoids. For this reason, COX-2 selective inhibitors (COXIBs) have been developed recently as anti-inflammatory agents to minimize the risk of GI toxicity. Recently, some COX-2 selective inhibitors have shown adverse cardiovascular side effects, resulting in the withdrawal of rofecoxib and valdecoxib from the market. Selective inhibition of COX-2 without reducing COX-1-mediated thromboxane production could alter the balance between prostacyclin and thromboxane and promote a prothrombotic state, thereby explaining the observed COX-2 cardiovascular risk. In this review, we describe mechanisms for the production of pro-inflammatory eicosanoid mediators contributing to inflammation and summarize promising options for the prevention of inflammatory mediator formation and the therapeutic inhibition of pain and inflammation.

show abstract

Section: 1a Leukotriene-b 4 Receptorsmentioning

confidence: 99%

Section: 1a Leukotriene-b 4 Receptorsmentioning

confidence: 99%

Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers

Khanapure¹,

Garvey²,

Janero³

et al. 2007

CTMC

284

188

View full text Add to dashboard Cite

show abstract

“…Thus, specific [ 3 H]‐LTB 4 binding has been demonstrated in many tissues, including human polymorphonuclear leucocytes (PMNs) [ 117, 118]. Pharmacological evidence suggested that BLT‐receptors were G‐protein coupled [ 119–121], and the receptor was recently cloned from retinoic acid differentiated HL‐60 cells and functionally expressed in CHO cells [ 122]. Incidentally, the BLT‐receptor was originally cloned as an orphan receptor from a human B‐lymphoblast cDNA library [ 123].…”

Section: Biological Activities and Receptorsmentioning

confidence: 99%

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

Claesson¹,

1999

Journal of Internal Medicine

101

View full text Add to dashboard Cite

show abstract

“…LTB4 elicits these responses by activation of an inhibitory guanine-nucleotidebinding protein (G1)-coupled membrane receptor [3][4][5][6][7][8]. Radio-ligand binding studies and functional studies have demonstrated that the G,-protein-coupled receptor binds [3H]LTB4 with high affinity [9][10][11][12] and the Gi-protein-uncoupled receptor binds [3H]LTB4 with low affinity [1,[13][14][15].…”

Section: Introductionmentioning

confidence: 99%

“…The very first step toward that goal is to construct efficient methods and assay systems for the solubilization of the membrane-bound receptor protein for characterization and purification. We have recently reported that sheep lung membranes have abundant LTB4 receptors, and that the specificity of the receptor in sheep lung membranes is equivalent to that in human polymorphonuclear leucocytes (PMN) and lung membranes [8,10]. Removal purification.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the soluble leukotriene B4 receptor from sheep lung membranes

Votta

Keefer

Mong

1990

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

Leukotriene B4 (LTB4) is an arachidonate metabolite which elicits a variety of pro-inflammatory responses by activation of a guanine-nucleotide-binding protein-coupled membrane receptor. As a prelude to receptor isolation and purification, we have established assay methods for LTB4 receptor solubilization and characterization from sheep lung membranes.[3H]LTB4 binding to the soluble receptor was saturable, specific, protein-concentration-and time-dependent and reversible. Binding of [3H]LTB4 was enhanced by divalent cations and inhibited by sodium ions in a manner analogous to its binding to the human leukocyte membrane receptor. Saturation binding yielded a dissociation constant (Kd) of 0.50 + 0.05 nm and a receptor density (Bmax ) of 330 + 90 fmol/mg of protein for [3H]LTB4 binding to detergent-solubilized receptor. In competition experiments, the rank order of binding affinity was LTB4 > 20-OH-LTB4 > trans-homo-LTB4 > 6-trans-LTB4 > U-75302. Gel-filtration chromatography showed that the LTB4 receptor protein in the detergent micellar state has a molecular mass in the range 800-1000 kDa. These results demonstrate that the physiologically and pharmacologically important LTB4 receptor may be readily solubilized from sheep lung membranes without alteration in binding specificity and characteristics, suggesting that sheep lung membranes represent a rich source with which to pursue receptor isolation and purification.

show abstract

Transition of affinity states for leukotriene B4 receptors in sheep lung membranes

Cited by 16 publications

References 20 publications

Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers

Eicosanoids in Inflammation: Biosynthesis, Pharmacology, and Therapeutic Frontiers

Asthma and leukotrienes: antileukotrienes as novel anti‐asthmatic drugs

Characterization of the soluble leukotriene B4 receptor from sheep lung membranes

Contact Info

Product

Resources

About