[29] Receptors for PGI2 and PGD2 on human platelets

Siegl, Adelaide M.

doi:10.1016/0076-6879(82)86189-2

Cited by 18 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism gives rise to prostaglandin-concentration-dependent desensitization of cyclic AMP formation that is due to slow turn-off of adenylate cyclase through the inhibitory prostaglandin receptor rather than activation of phosphodiesterase activity, as time-dependent inhibition of cyclic AMP formation occurs in the presence of phosphodiesterase inhibitors [3]. The mechanism is supported by radioligand binding studies which indicate that there are two classes of prostaglandin binding site on platelet membranes [5][6][7]. The proposed mechanism is further supported by our ability to mathematically model platelet cyclic AMP metabolism over a wide range of prostaglandin concentrations using a simple scheme involving rapid activation of adenylate cyclase, followed by slow, reversible transition of adenylate cyclase to an inactive form (desensitization) through a distinct inhibitory receptor [3].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin-concentration-dependent desensitization of adenylate cyclase in human erythroleukaemia (HEL) cells is abolished by pertussis toxin and enhanced by induction by dimethyl sulphoxide

Ashby

Almonor

Wernick

et al. 1991

Biochemical Journal

View full text Add to dashboard Cite

Prostaglandin-regulated cyclic AMP metabolism in human erythroleukaemia (HEL) cells was similar to that previously described in platelets [Ashby (1989) Mol. Pharmacol. 36, 866-873], displaying prostaglandin-concentration-dependent desensitization that could be explained by the presence of separate stimulatory and inhibitory prostaglandin receptors. Pertussis toxin abolished prostaglandin-concentration-dependent desensitization, indicating that the process is mediated through a pertussis toxin-sensitive GTP-binding protein. Treatment of HEL cells for 4 days with the inducer dimethyl sulphoxide enhanced prostaglandin-concentration-dependent desensitization, but did not alter the initial rate of cyclic AMP synthesis or the amount of Gi2 alpha measured by immunoblotting, suggesting that the inhibitory receptor was selectively induced by changing the cells to a more platelet-like form.

show abstract

Section: Introductionmentioning

confidence: 99%

Prostaglandin-concentration-dependent desensitization of adenylate cyclase in human erythroleukaemia (HEL) cells is abolished by pertussis toxin and enhanced by induction by dimethyl sulphoxide

Ashby

Almonor

Wernick

et al. 1991

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Both are thought to bind, although with probably slightly different affinities, to the same receptor (Siegl, 1982;Virgolini et al, 1988). As shown in Table 1, MMR upregulation by PGE1 or PGE2 is virtually identical.…”

Section: Resultsmentioning

confidence: 98%

Prostaglandin E specifically upregulates the expression of the mannose-receptor on mouse bone marrow-derived macrophages.

et al. 1990

View full text Add to dashboard Cite

The macrophage mannose receptor (MMR) facilitates the binding and internalization of microorganisms and glycoproteins with terminal mannose residues. The receptor is progressively upregulated as bone marrow precursor cells mature into macrophages and thus may serve as a marker of differentiation. Prostaglandins of the E series (PGE) are known inhibitors of monocyte and macrophage precursor proliferation, an effect often associated with cellular maturation. MMR expression was therefore assessed after exposure of bone marrow macrophage precursor (BMMP) cells to these prostanoids. Receptor expression was determined by ligand binding and via immunoprecipitation of newly synthesized receptor molecules. PGE1 and PGE2 at 10(-9)-10(-6) M upregulated MMR surface expression and biosynthesis four- to sixfold in a dose-dependent manner. BMMPs responsive to prostaglandins were characterized by plastic adherence, F4/80 antigen expression, and nonspecific esterase activity. Prostaglandins accelerated the expression of the MMR in cells by 48-72h, with maximal levels of receptor expression being identical in control or treated cells. Thus, prostaglandins enhanced mannose receptor expression in adherent but not fully differentiated macrophage precursors. This effect is specific for PGE and is mimicked by dibutyrl cyclic AMP. These results indicate that prostaglandins accelerate MMR expression and hence the differentiation of macrophage precursor cells. Cells resident in the bone marrow secrete abundant prostaglandins, suggesting that a paracrine mechanism may exist to regulate MMR expression and function.

show abstract

“…Platelet-rich plasma was prepared from citrated whole human blood (Siegl 1982), treated with 1150th its volume of 50 rnM EDTA, and centrifuged at 4000 x g for 20 min. The pellet was suspended in 0.1 M Tris, 0.1 M potassium phosphate at pH 8.2 containing 20 pM indomethacin for a final cell concentration of 1.5 x 1 0 8 / m~.…”

Section: Human Platelet 12 -1ipoxygenasementioning

confidence: 99%

L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor

Bélanger¹,

Maycock²,

Guindon³

et al. 1987

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol) was a potent inhibitor of leukotriene biosynthesis in intact rat and human leukocytes and CXBG mastocytoma cells (IC50 values, 18-240 nM) and of crude human leukocyte and highly purified porcine leukocyte 5-lipoxygenase (IC50 value, 4 X 10(-7) M). The selectivity of L-656,224 for 5-lipoxygenase was shown through the relative lack of activity of the compound on 12-lipoxygenase, 15-lipoxygenase, cyclooxygenase, catalase, and myeloperoxidase. The compound showed (i) oral activity against hyperalgesia induced in the rat paw by injection of yeast or platelet-activating factor, (ii) dyspnea in sensitized inbred rats induced by an aerosol of antigen, and (iii) bronchoconstriction induced by an aerosol of Ascaris in squirrel monkeys, suggesting a role for 5-lipoxygenase inhibitors in the treatment of asthma and peripheral pain.

show abstract

[29] Receptors for PGI2 and PGD2 on human platelets

Cited by 18 publications

References 11 publications

Prostaglandin-concentration-dependent desensitization of adenylate cyclase in human erythroleukaemia (HEL) cells is abolished by pertussis toxin and enhanced by induction by dimethyl sulphoxide

Prostaglandin-concentration-dependent desensitization of adenylate cyclase in human erythroleukaemia (HEL) cells is abolished by pertussis toxin and enhanced by induction by dimethyl sulphoxide

Prostaglandin E specifically upregulates the expression of the mannose-receptor on mouse bone marrow-derived macrophages.

L-656,224 (7-chloro-2-[(4-methoxyphenyl)methyl]-3-methyl-5-propyl-4-benzofuranol): a novel, selective, orally active 5-lipoxygenase inhibitor

Contact Info

Product

Resources

About