Disease relevance of BW245C

• Using a murine model of atopic dermatitis, a chronic Th2-type allergic inflammatory disease, we demonstrate that the potent DP1 agonist BW245C dramatically decreases the Ag-specific T cell activation in the skin draining lymph nodes and markedly prevents the skin lesions following repeated epicutaneous sensitization with OVA [1].
• The TP receptor agonist 11alpha,9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid (U46619) induced emesis at doses as low as 3 microg/kg, i.p. but the DP receptor agonist 5-(6-Carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin (BW245C) was approximately 1000 times less potent [2].

High impact information on BW245C

• By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD(2)- and NA-induced vasodilation [3].
• PGD2 and BW 245C also increased cAMP levels in Chinese hamster ovary cells expressing the receptor, in a concentration-dependent manner [4].
• Finally, we demonstrate that BW245C, but not DK-PGD(2), can delay the onset of apoptosis in cultured eosinophils, presumably through interaction with DP [5].
• These effects are induced by the CRTH2-selective agonist 13-14-dihydro-15-keto-PGD(2) (DK-PGD(2)) but not by the DP-selective agonist BW245C [5].
• This effect was mimicked by the DP1-selective agonist BW245C but not by the PGD(2) metabolite 15d-PGJ(2), suggesting that neuroprotection was mediated by the DP1 receptor [6].

Biological context of BW245C

• Behavioural, ECoG spectrum power and body temperature effects of BW 245C, a prostaglandin analogue after intraventricular microinjection in chicks [7].
• BW 245C (an agonist for PGD (DP) receptor) blocked the allodynia with an IC50 of 83 ng kg(-1) [8].
• 2 Intravenous BW 245C (1,2 and 4 ng kg-1 min-1) produced a progressive increase in heart rate and pulse pressure in four healthy male volunteers [9].
• The inhibitory effects of both PGD2 and BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 microM) [10].
• Prostaglandin D2 (PGD2) and the selective DP receptor agonist BW 245C have been previously shown to lower intraocular pressure in rabbits, while PGD2, but not BW 245C, caused plasma extravasation, eosinophil infiltration, and goblet cell depletion [11].

Anatomical context of BW245C

• Previous studies on prostanoid-induced blood-aqueous barrier disruption have been predominantly restricted to studies on natural prostanoids and the highly selective DP-receptor agonist BW245C, which was inactive [12].
• Although BW 245C was equipotent to PGD2 as an ocular hypotensive agent, it did not cause pathological effects in the conjunctiva [13].
• In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE-mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist [14].
• Colonic granulocyte infiltration was significantly reduced by administration of prostaglandin D(2) or a DP receptor agonist (BW-245C) [15].
• PGD2 and BW245C did not relax contracted human pulmonary arteries [16].

Associations of BW245C with other chemical compounds

• PGE1 at 280 nM and BW245C at 7.7 nM induced a significant PA inhibition in PRP and washed platelets (though less pronounced by PGE1) concomitant to a very large increase (8-13-fold) in platelet c-AMP level both in PRP and washed platelets [17].
• PGD2 induced a dose-related antagonism of the inhibitory actions of BW245C, prostacyclin and carbacyclin on guinea-pig platelets [18].
• 4. Analyses of BW 245C- and PGD2-mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C [19].
• BW245C also inhibited O2- release, and this inhibition was antagonized competitively by the DP-receptor blocking drug, AH6809 (pA2 6.6) [20].
• L-644,698 is, therefore, comparable to those agonists with known efficacy at the DP receptor (EC50): PGD2 (0.5 nM), ZK 110841 (0.2 nM) and BW245C (0.3 nM) [21].

Gene context of BW245C

• Prostaglandin E2 and BW 245C (a synthetic DP receptor agonist) decreased OPG in the supernatants of human osteoblasts but not in immortalized cell lines [22].
• Mutation of Ser(329) to Ala(329) within a consensus PKA site in TP alpha rendered the mutant TP alpha(S329A) insensitive to BW245C-mediated desensitization [23].
• 9 beta-PGD2 and BW245C antagonized competitively the contractile action of PGD2 [24].
• Both PGE(2) and the DP(1) receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] strongly inhibited DP(2) receptor-mediated CD203c expression [25].
• The potency ranking for depolarization was BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin; DP-selective, EC50=0.14 microM)>prostaglandin E2 (nonselective EP agonist)>U-46619 (11alpha, 9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid; TP agonist)>prostaglandin F2alpha (FP receptor agonist) [26].

Analytical, diagnostic and therapeutic context of BW245C

• Heart rate, derived from the ECG, was significantly (p less than 0.05) higher and pre-ejection period significantly (p less than 0.05) shorter on BW245C at 1 h after dosing on each day [27].

References