Stimulation of histamine release by the peptide kinetensin

The peptide kinetensin isolated from pepsin-treated human plasma induced a dose-dependent release of histamine when exposed to rat peritoneal mast cells. The threshold concentration was around 10(-6) M, the ED50 was 10(-5) M, and the optimal concentration of between 10(-4) to 10(-3) M released 80% of the total histamine. Kinetensin was 10 to 100 times less potent than neurotensin and equipotent with the opioid peptide dynorphin. The histamine release was clearly temperature-dependent, with no release occurring at 0 degrees or 45 degrees C and with an optimum around 37 degrees C. The histamine release was significantly reduced in the absence of extracellular calcium. Kinetensin also induced a dose-dependent increase in vascular permeability when injected intradermally into rats. The findings indicate that kinetensin is a potent histamine releaser in the rat and may serve as an inflammatory mediator.     

Comparison of neuromedin-N and neurotensin on net fluid flux across rat small intestine

Neuromedin-N, a hexapeptide recently isolated and purified from porcine spinal cord, has close sequence homology with the C-terminal region of the tridecapeptide neurotensin. Both peptides have a remarkably similar peripheral distribution. Little is known of the biological activity of neuromedin-N. Neurotensin and peptide histidine methionine are known to stimulate net fluid secretion into rat small intestine. We have therefore tested the effect of neuromedin-N and the hexapeptide neurotensin-(8-13), the smallest fully active analogue of neurotensin in this system, compared with that of neurotensin and peptide histidine methionine. All four peptides reduced net absorption in low doses and caused net secretion in larger doses. However, whereas peptide histidine methionine was active in all areas of the small intestine, neurotensin, neurotensin-(8-13) and neuromedin-N were inactive in the duodenum. In the post-duodenal areas neurotensin was approximately 7 times more active than peptide histidine methionine, 21 times more potent than neuromedin-N and 33 times more potent than neurotensin-(8-13).     

Interaction of neurotensin with the substance P receptor mediating histamine release from rat mast cells and the flare in human skin.

1 Substance P induced histamine release from rat peritoneal mast cells in a dose-dependent manner over the concentration range 1 to 10 microM. 2 At concentrations in the range 2.5 to 1 0 microM, neurotensin produced only about 5% release of histamine, which was substantially less than the maximum effect obtained with substance P. 3 Neurotensin, 2.5 to 10 microM produced graded inhibition of histamine release induced by substance P. The inhibitory effect of neurotensin was not seen when histamine release was induced by an antigen-antibody effect of neurotensin was not seen when histamine release was induced by an antigen-antibody reaction or by the ionophore, A 23187. Some evidence was obtained to suggest that compound 48/80 may interact with the same receptor as substance P and neurotensin. 4 [D-Arg8]neurotensin, [D-Arg9]neurotensin, xenopsin and the C-terminal octapeptide of substance P (SP4-11) all inhibited histamine release by substance P, but physalaemin did not. 5 Neurotensin inhibited the wheal and flare reactions induced by substance P in human skin. 6 [D-Trp7,9]substance P released histamine from rat mast cells and was about 12 times more potent than substance P itself. [D-Trp7,9]SP1-11 also produced wheal and flare responses in human skin, being 1.8 times more potent than substance P in the production of flare.     

Intradermal application of nociceptin increases vascular permeability in rats: the possible involvement of histamine release from mast cells

Intradermal application of nociceptin was used to investigate its in vivo effect on the inflammatory response in rats. Intradermal nociceptin (5 pmol/site-5 nmol/site) increased vascular permeability in a dose-dependent manner. The increased vascular permeability by nociceptin (5 nmol/site) was dose-dependently inhibited by the histamine H1 receptor antagonist pyrilamine (50 pmol/site-5 nmol/site). In rat peritoneal mast-cell preparation, nociceptin (10(-8)-10(-4) M) dose-dependently stimulated histamine release. The effect of nociceptin (10(-5) M) occurred rapidly (within 30 s) and was inhibited by pertussis toxin, Ca2+, but was not sensitive to naloxone, a classical opioid receptor antagonist. These characteristics are in agreement with features of the opioid-receptor-like 1 (ORL1) receptor, a non-classical opioid receptor linked to a pertussis toxin-sensitive G protein. Taken together, these data suggest that nociceptin, likely acting via the ORL1 receptor at the site of inflammation, might be critical for the enhancement of the inflammatory response by stimulating histamine release from mast cells.     

Pharmacological activity of bamifylline on lung anaphylaxis: in vitro studies.

Bamifylline, a 7-8 disubstituted theophylline derivative, reduces in a dose dependent way (1 x 10(-5) M, 1 x 10(-4) M and 1 x 10(-3) M) the release of histamine, TXB2 (measured also as TXA2-like material) and SRS-A (as LTD4-like material) during the immunological challenge of actively sensitized guinea-pig lungs perfused in vitro. Theophylline was significantly less potent than bamifylline and particularly, at the higher concentrations used (1 x 10(-3) M), bamifylline was 2.7 times more potent than theophylline in reducing the immunological release of histamine and 1.6 and 1.5 times more potent in inhibiting the production of TXB2 and SRS-A, respectively. These data suggest that the ability of the two xanthine derivatives to control the immunological release of histamine represents an important point in understanding the mechanism of their anti-anaphylactic activity.     

Inhibitory effects of Moutan cortex on immediate allergic reactions

The anti-allergic effect of an ethanol extract from Moutan Cortex was evaluated in some animal models. The Moutan Cortex extract (30, 100 mg/kg, i.p.) dose-dependently inhibited systemic anaphylactic shock induced by compound 48/80 in mice. It also inhibited dose-dependently the scratching behavior induced by compound 48/80 or histamine at a dose of 100 mg/kg. An increase in the vascular permeability induced by compound 48/80 or histamine was also inhibited by the Moutan Cortex. In addition, in vitro studies, the Moutan Cortex inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. To investigate the active component of Moutan Cortex extract, it was suspended in water and extracted with EtOAc to yield EtOAc insoluble (A) and soluble (B) fractions. The effect of extract (B) was more potent than that of extract (A) in inhibiting histamine release. From these findings, it seems likely that the Moutan Cortex extract is effective in antagonizing certain pharmacological effects induced by compound 48/80, which is probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on histamine. The main active component of Moutan Cortex is considered to be contained in extract (B). In conclusion, Moutan Cortex may be useful for the relief of symptoms of atopic dermatitis and other allergy-related diseases.     

Antiallergic effects of mequitazine. 1. In vitro experiments

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).     

Cardiac electrophysiologic effects of a new calcium antagonist, lacidipine.

Lacidipine is a new 1,4-dihydropyridine derivative with potent and long-lasting antihypertensive activity. We used intracellular microelectrodes to characterize the electrophysiologic properties of lacidipine on different cardiac preparations. Lacidipine (10(-8) -10(-6) M) dose-dependently decreased contractility of driven sheep Purkinje fibers. For concentrations less than or equal to 10(-7) M, this effect was associated with a selective decrease of the plateau height. Higher concentrations (3 X 10(-7) and 10(-6) M), however, affected action potential amplitude, overshoot, and maximum rate of depolarization. In the same range of concentrations, lacidipine did not affect normal automaticity of guinea-pig sinus node and sheep Purkinje fibers. Lacidipine (10(-6) M) consistently blocked barium-induced abnormal automaticity in Purkinje fibers and reduced the amplitude and Vmax of the slow action potentials induced by histamine (10(-5) M) in guinea pig papillary muscle depolarized by potassium (22 mM). The effect of lacidipine on the slow inward current (Isi) was studied in shortened Purkinje fibers under voltage-clamp conditions. Lacidipine (10(-7)-10(-6) M) reduced the Isi without affecting the I-V relationship. None of the effects of lacidipine was reversed by 2-h washout. The results indicate that lacidipine has calcium-antagonistic properties in cardiac tissues. Its cardiac effects occur at concentrations 100 times higher than those active in the vascular smooth muscle. The lack of recovery of the lacidipine effects suggests that its interaction with the calcium channel may occur at an inner site of the cell membrane.     

Antiallergic effect of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidaz ole difumarate (KB-2413)

Antiallergic effects of 1-(2-ethoxyethyl)-2-(4-methyl-1-homopiperazinyl)benzimidazol e difumarate (KB-2413) were investigated in immediate type hypersensitivities. KB-2413 (0.005-0.04 mg/kg p.o.) showed a marked inhibition on lethal anaphylaxis in guinea pigs induced by anti-egg albumin rabbit serum, and it was 30 and 1.6 times more potent than chlorpheniramine and ketotifen, respectively. KB-2413 (0.003-0.1 mg/kg p.o.) showed a dose-dependent inhibition on vascular permeability increase induced by 48 h homologous passive cutaneous anaphylaxis (PCA) and histamine in guinea pigs, being about 10-30 times and 3 times more potent than chlorpheniramine and ketotifen, respectively. All drugs did not completely inhibit 4 h heterologous PCA in guinea pigs induced by the anti-egg albumin rabbit serum in the doses used here, but KB-2413 was more effective than chlorpheniramine and ketotifen. No difference in inhibitory effect on the vascular permeability increase between the single and daily oral administration for 4 weeks of KB-2413 could be found. KB-2413, as well as chlorpheniramine and ketotifen, showed a dose-dependent inhibition on 48 h homologous PCA in rats at doses of 1-10 mg/kg p.o., and showed a concentration-dependent inhibition on Schultz-Dale reaction at 10(-8) - 10(-7) mol/l. KB-2413 (10(-5) - 10(-3) mol/l) showed a concentration-dependent inhibition of anaphylactic histamine release from isolated rat peritoneal mast cells which were passively sensitized by rat IgE. KB-2413 also inhibited compound 48/80-induced histamine release from rat peritoneal mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pinusolide from the leaves of Biota orientalis as potent platelet activating factor antagonist

We investigated the effect of a new PAF antagonist pinusolide, isolated from the leaves of Biota orientalis, on PAF-induced [3H]serotinin release from rabbit platelets, hypotension and vascular permeability. Pinusolide (IC50, about 5 x 10(-6) M) inhibited specifically [3H]serotinin release from rabbit platelets when stimulated with PAF (5 x 10(-8) M), but showed no effect when induced by ADP, collagen, and thrombin. It also inhibited PAF-induced hypotension in a dose-dependent manner in rats with no effect on the hypotension induced by acetylcholine, histamine and serotonin. The inhibitory effect of pinusolide on the PAF-induced vascular permeability is less specific than the induced hypotension. These results suggest that pinusolide may prove of therapeutic value in the treatment of hypotension and a molecular design of pinusolide analogues may provide the possibility of a new PAF specific antagonists.     

Effects of beta-endorphin on rat mast cells

The endogenous opioid peptide beta-endorphin induced a dose-dependent release of histamine from rat peritoneal mast cells. The threshold concentration was around 10(-6) M and the optimal concentration of 2 X 10(-5) M released 35% of the total histamine. The release of histamine was very rapid, complete within 10 s, and very similar to that induced by neurotensin or compound 40/80. The histamine release was temperature dependent and inhibited at increased extracellular calcium concentrations. Taken together, the findings indicate that the release of histamine induced by beta-endorphin is a specific, energy-dependent process. The pattern of release has much in common with that induced by other basic peptides, such as neurotensin, dynorphin and substance P.     

Biochemical and pharmacological characterization of ICI 198,615: a peptide leukotriene receptor antagonist

ICI 198,615 is one representative of a new chemical class of peptide leukotriene receptor antagonists that are the most potent and selective described to date. ICI 198,615 antagonized LTC4-, LTD4- and LTE4-induced increases in cutaneous vascular permeability in the guinea pig, with i.v. ED50 values of 0.083, 0.11 and 0.067 mumol/kg, respectively. Against LTD4, ICI 198,615 was 615 and 415 times more potent than LY 171883 and FPL 55712, respectively. L-Serine borate, an inhibitor of the metabolism of LTC4 to LTD4, did not influence the antagonism by ICI 198,615 of LTC4-induced increases in cutaneous vascular permeability. The compound both inhibited and reversed aerosol ovalbumin antigen-induced increases in pulmonary resistance in passively sensitized guinea pigs, but demonstrated little ability to inhibit or reverse ovalbumin antigen-induced decreases in dynamic lung compliance. At concentrations ranging from 10(-8) to 10(-5) M, ICI 198,615 had no significant effect on either the spontaneous or ovalbumin antigen-induced release of histamine, peptide leukotrienes, thromboxane B2 or 6-keto-prostaglandin F1 alpha from chopped guinea pig lung. At 10 microM, the compound did not inhibit 5-, 12- or 15-lipoxygenase. Finally, ICI 198,615 antagonized LTD4-induced increases in TxB2 release from chopped guinea-pig lung.     

Antipruritic and antierythema effects of ascomycete Bulgaria inquinans extract in ICR Mice

The effect of ethanol extract obtained from Bulgaria inquinans on the scratching behavior and vascular permeability changes induced by compound 48/80, histamine and serotonin in ICR mice was studied. The extract dose-dependently inhibited scratching behavior induced by compound 48/80 and serotonin. A significant inhibition was observed at doses of 300 and 600 mg/kg when Bulgaria inquinans extract was administered orally. However, no inhibitory effect was observed on the histamine-induced scratching behavior by the extract, even at a dose of 600 mg/kg. In addition, it also inhibited the increase in the vascular permeability induced by compound 48/80 and serotonin at doses of 300 and 600 mg/kg; however, it failed to inhibit the increased vascular permeability induced by histamine, even at a dose of 600 mg/kg. Bulgaria inquinans extract showed a potent inhibitory effect on histamine release induced by compound 48/80. These results suggest that Bulgaria inquinans extract is effective in cutaneous pruritus and erythema, which were probably mediated by inhibiting the release of histamine from mast cells and antagonizing the effect on serotonin.     

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions

Since a newly synthesized nonsteroidal antiinflammatory drug (NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid (CN-100), was found to markedly inhibit rat paw edema induced by carrageenin and other phlogists, the effects of the drug on other acute inflammatory reactions and prostaglandins (PGs)-related reactions were compared with those of known NSAID in this study. At even a large dose of CN-100, 20 mg/kg, the drug did not significantly inhibit the increased vascular permeability induced by histamine in rat skin, but CN-100 could dose-dependently inhibit the increased vascular permeability induced by acetic acid in mouse peritoneum. The inhibitory activity of CN-100 in the latter was equivalent to that of pranoprofen and indometacin. CN-100 exerted a potent inhibitory action on erythema induced by UV irradiation, which was equal to and 3 times stronger than pranoprofen and indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of CN-100 on reactions relevant to PGs were examined. The drug at dose levels lower than antiinflammatory doses could prevent acute death and diarrhea induced by i.v. injection of arachidonic acid in rabbits and endotoxin in mice, respectively, suggesting that the drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of pranoprofen and indometacin.     

Structure-activity relationship in the mast cell degranulating capacity of neurotensin fragments

The mast cell degranulating capacity of neurotensin and three of its fragments was examined. In Tyrode solution (137 mM NaCl, 2.7 mM KCl, 0.4 mM NaH2PO4, 1.4 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, 5.6 mM glucose, pH 7.4), neither intact neurotensin nor its C-terminal tripeptide (Tyr-Ile-Leu) caused any release of histamine. Concentrations of neurotensin exceeding 10(-4)M did cause histamine release but through lysis of the cells. The C-terminal hexa- and octapeptides of neurotensin (Arg-Arg-Pro-Tyr-Ile-Leu and Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, respectively) induced a non-cytolytic release of histamine with the latter peptide being more active (ED50 = 90 microM for the hexapeptide and 13 microM for the octapeptide). This release was not affected by the C-terminal tripeptide. It was found to be calcium-dependent and was inhibited by the anti-allergic drug, disodium cromoglycate. Phosphatidylserine did not enhance release of histamine and saturation of the immunoglobulin E (IgE) receptors did not inhibit it.     

Anthracycline-induced histamine release from rat mast cells

Comparisons were made of the ability of doxorubicin, daunorubicin, rubidazone and aclacinomycin A to release histamine from rat peritoneal mast cells. Preliminary in vitro experiments indicated that doxorubicin (10(-6) to 2.5 X 10(-4) M), in contrast to compound 48/80 and the calcium ionophore A23187, did not produce significant release under any condition tested when purified or unpurified rat mast cells were used. In in vitro experiments, released histamine was measured in the cell-free supernatant of peritoneal fluid of rats after intraperitoneal injection of the agents. The time course of doxorubicin-induced histamine release from the peritoneum was rapid, with maximal release occurring within 4 to 6 min. Dose-response curves of the 4 agents over the range 10(-5) to 3.3 X 10(-3) M revealed that all caused histamine release, with 10(-3) M concentrations of each causing maximal release of comparable magnitude to that produced by 9.5 X 10(-6) M A23187. Treated mast cells recovered from the peritoneal cavity showed degranulation and vacuolization when examined by electron microscopy. Increased vascular permeability by the Evans-blue test was also noted with all 4 agents, and zones were of comparable size after injection of the highest concentration of each agent. The results indicate that in vivo, doxorubicin, daunorubicin, rubidazone and aclacinomycin A cause a rapid release of histamine from rat mast cells and an increase in vascular permeability in rat sin. There also appeared to be a reasonable correlation between the blueing reaction and histamine release in the peritoneal cavity in that the doses that did not cause skin blueing also failed to cause histamine release. The lack of histamine release by doxorubicin from mast cell preparations in vitro suggests that alterations to the doxorubicin molecule or the presence of other critical substances may be necessary for this activity to commence.     

Potent inhibitory activity of HSR-6071, a new antiallergic agent, on passive cutaneous anaphylaxis (PCA).

Antiallergic effects of 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (HSR-6071), a newly synthesized agent, were investigated. The 48-hr homologous passive cutaneous anaphylaxis (PCA) in rats was inhibited in a dose-dependent manner by i.v. and p.o. administration of the agent (ED50 = 0.0096 mg/kg and 0.18 mg/kg, respectively). The IgE-mediated histamine release from rat peritoneal exudate cells was inhibited by HSR-6071, with an IC50 of 4.6 x 10(-10) M. Regarding the non-immunological histamine release, HSR-6071 inhibited compound 48/80-induced, but not A23187-induced and spontaneous histamine release. On the other hand, an increase in vascular permeability induced by histamine, serotonin and bradykinin was unaffected by HSR-6071 in doses sufficient to inhibit PCA. In addition, the contractile responses of isolated guinea pig ileum to histamine, acetylcholine and serotonin were also unaffected by the agent even in a high concentration of 10(-4) M. These results indicate that HSR-6071 possesses a potent antiallergic activity and that the inhibition of PCA by HSR-6071 may be due to the suppression of chemical mediators release from mast cells.     

Forskolin inhibits the release of histamine from human basophils and mast cells

We found that forskolin (10(-7) to 3 X 10(-5) M) caused dose-related inhibition of antigen-induced histamine release from human basophil leukocytes. The dose-response inhibition curve was paralleled by a forskolin-induced increase in cyclic AMP (cAMP) levels in human leukocyte preparations. The kinetics of inhibition of histamine release and of the increase in leukocyte cAMP were the same. In a second series of experiments we evaluated the effect of forskolin on antigen-induced histamine release from chopped human lung passively sensitized with serum from an allergic patient. Forskolin (10(-7) to 3 X 10(-5) M) dose-dependently inhibited the release of histamine from human lung mast cells. Thus forskolin appears to modulate the release of mediators of the immediate hypersensitivity reaction, presumably through activation of adenylate cyclase in human basophils and mast cells.     

Effect of histamine on the T-cell colony formation of PHA-stimulated cells

The effect of histamine on T-cell colony formation was studied in human peripheral blood mononuclear cells. Histamine inhibited dose-dependently (10(-4)-10(-6) M) the colony formation of PHA-stimulated T-cells. The inhibition was similar in normal controls and rheumatoid arthritis (RA) patients in spite of the fact that in RA the colony formation was significantly lower than in the normal controls. No increase of colony formation was observed at low concentrations (less than 10(-7) M). Impromidine was less effective than histamine, and pyridylethylamine (PEA) was inactive. Cimetidine counteracted the effect of histamine while chlorpheniramine did not. The results show that colony formation may be inhibited through H2-receptors. This action may be of importance in cellular interactions in tissues with high local histamine concentrations.     

Characterization of prostanoid receptors mediating inhibition of histamine release from anti-IgE-activated rat peritoneal mast cells

1. Prostanoid receptors mediating inhibition of anti-IgE induced histamine release from rat peritoneal mast cells have been characterized pharmacologically. PGD2 and the specific DP receptor agonists BW 245C and ZK 118182 were the most potent inhibitors with half-maximal concentrations of 0.26, 0.06 and 0.02 microM respectively. The maximum inhibition attainable was 60-65% with 10(-5) M BW 245C and ZK 118182. 2. Among several EP receptor agonists investigated, only PGE2 and the EP2/EP3 receptor agonist misoprostol induced significant inhibition (46.8 +/- 4.7% at 10(-4) M and 18.7 +/- 6.8% at 10(-5) M respectively). The IP receptor agonists cicaprost and iloprost were both less potent than the DP agonists in inhibiting histamine release (45.2 +/- 3.3% and 35.1 +/- 2.5% inhibition respectively at 10(-5) M), whereas PGF2 alpha and the TP receptor agonist U-46619 were only marginally effective. 3. The EP4/TP receptor antagonist AH 23848 failed to affect the inhibitory actions of PGD2 or PGE2 even at 10(-5) M, whereas the DP/EP1/EP2 receptor antagonist AH 6809 slightly enhanced the effect of PGD2 at 10(-6) M. 4. At concentrations of 3 x 10(-6) to 10(-5) M, the putative DP receptor antagonist ZK 138357 dose-dependently suppressed the inhibitory activities of the DP agonists, PGE2 and cicaprost. The antagonism of ZK 138357 against the DP receptor agonists appeared to be competitive with pA2 values of around six. 5. In conclusion, these data support our earlier proposal that an inhibitory DP receptor is the predominant prostanoid receptor in rat peritoneal mast cell. The properties of this receptor in relation to putative DP receptor subtypes reported in the literature are discussed.