A novel inhibitory prostanoid receptor in piglet saphenous vein

Coleman, Robert A.; Grix, S.P.; Head, Sarah A.; Louttit, James B.; Mallett, Anthony I.; Sheldrick, R.L.G.

doi:10.1016/0090-6980(94)90084-1

Cited by 259 publications

(223 citation statements)

References 16 publications

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“…This increase in cAMP was inhibited by the EP4 specific antagonist AH23848. This antagonist was initially described as a competitive antagonist of PGE2 at EP4 receptors with low affinity (pA2 5.36) but high selectivity [25]. In Jurkat, KM-3 and U-937 cell membranes, however, it did not behave as a true competitive antagonist.…”

Section: 3 Functional Pge2 Receptors Of the Ep4 Subtype On Human Mmentioning

confidence: 99%

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

1996

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Section: 3 Functional Pge2 Receptors Of the Ep4 Subtype On Human Mmentioning

confidence: 99%

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

1996

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“…Several PGs, specifically PGD 2 (32,33), PGI 2 (21), and PGE 2 (by means of the EP 2 and EP 4 receptors) (34,35), can elicit vasodilatory effects. Morrow et al (17) showed that, within a few minutes of ingestion of NA, circulating PGD 2 and its metabolite, 9␣,11␤-PGF 2 , were increased several hundred-fold in normal humans.…”

Section: Na-induced Flush-like Responses Have Previously Been Reportementioning

confidence: 99%

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

Cheng¹,

Wu²,

Wu³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

263

188

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Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2 ؊/؊ mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2-and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1 ؉/؉ , DP1 ؉/؊ , and DP1 ؊͞؊ mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP ؊͞؊ mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.aspirin ͉ prostaglandin D2 receptor 1 antagonist ͉ MK-0524 ͉ niacin ͉ flushing N icotinic acid (NA), sometimes called niacin, is a watersoluble B vitamin that has been used to treat dyslipidemia for almost 50 years (1, 2). Used in high doses, it reduces plasma low-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipoprotein(a) and increases high-density lipoprotein cholesterol and apolipoprotein A-I (3, 4). NA has been shown to have cardiovascular benefit when used alone or in combination with statins (hydroxymethylglutaryl-CoA reductase inhibitors) in several clinical trials (5-7).Despite these demonstrated beneficial effects, widespread use of NA for dyslipidemia has been limited by symptoms of flushing, which is associated with cutaneous vasodilation of the face, neck, and torso that occurs in nearly all patients (5, 8). Administration of cyclooxygenase (COX) inhibitors, such as aspirin and indomethacin, before ingestion of NA can attenuate the NA-induced cutaneous reactions in most patients (9-13) without affecting its plasma free fatty acid-lowering effect (14). However, doses of aspirin of 325 mg or higher are generally required to significantly block flushing (15), which compromises the utility of this approach for the chronic suppression of flushing. Although the mechanism of action of NA-induced flushi...

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“…Guanine nucleotides can reduce the affinity of PGE2 binding to the EP2 receptor, suggesting that this receptor is coupled to Gs . The EP4 receptor, like the EP2 receptor, is positively coupled to adenylate cyclase ( Coleman et al, 1994). PGE2 can strongly inhibit adenylate cyclase in CHO cells expressing the EP3 receptor, and this inhibition can be completely blocked by pertussis toxin (PT) treatment, indicating that EP3 is coupled to a PT-sensitive Gi protein (Sugimoto et al, 1992).…”

Section: Signal Transduction For Pge2 Receptorsmentioning

confidence: 99%

“…Distinct receptors have been identified for each of the five naturally occurring prostanoids, PGE2, PGF2a., PGD2, PGii and TxA2 by using pharmacological comparisons of agonist and antagonist potency, and biochemical ligandbinding studies, and analyzing PG-induced signal transduction in cells (Coleman et al, 1990). These studies suggest that the prostanoid receptor is a receptor coupling via a G protein to effectors such as adenylate cyclase and phospholipase C. In the case of PGE2 receptors, four subtypes have currently been identified, namely EPl, EP2, EP3, and EP4 (Coleman et al, 1990(Coleman et al, , 1994. EPl subtype is coupled to Ca 2 + mobilization, EP2 and EP4…”

Section: Prostanoid Receptorsmentioning

confidence: 99%

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

Qian¹

1997

Insect Biochemistry and Molecular Biology

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A novel inhibitory prostanoid receptor in piglet saphenous vein

Cited by 259 publications

References 16 publications

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

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A novel inhibitory prostanoid receptor in piglet saphenous vein

Cited by 259 publications

References 16 publications

Exclusive expression of the Gs‐linked prostaglandin E2 receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Exclusive expression of the Gs‐linked prostaglandin E2 receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Antagonism of the prostaglandin D 2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

Contact Info

Product

Resources

About

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Exclusive expression of the Gs‐linked prostaglandin E₂ receptor subtype 4 mRNA in human mononuclear Jurkat and KM‐3 cells and coexpression of subtype 4 and 2 mRNA in U‐937 cells

Antagonism of the prostaglandin D ₂ receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans