Disease relevance of p-Methoxy-N-methylphenethylamine

• Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls [1].
• In addition, this form of SCF induced the expression of a pertussis toxin-sensitive G(i) protein, G(i3) that interacts with MBP to trigger mast cell non-IgE-dependent activation in a manner similar to other cationic compounds such as compound 48/80 [2].
• Mast cell degranulating agents polymyxin B and, to a lesser degree, compound 48/80 produced significant peritoneal eosinophilia after 6-8 wk of weekly intraperitoneal injections (p less than or equal to 0.05) [3].
• In contrast, mast cell degranulation produced by several days of treatment with the cationic secretagogue compound 48/80, while also increasing basal NGF levels, prevented a further increase in NGF levels and attenuated hypersensitivity during inflammation [4].
• Treatment of neonatal rats with the alternate degranulating agent compound 48/80 was found to induce a limited CTMC but not a MMC hyperplasia [5].

Psychiatry related information on p-Methoxy-N-methylphenethylamine

• A significant time-response relationship was observed between the pretreatment time of Hoe 498 at a dose of 4.0 mg/kg and the inhibition of compound 48/80-induced water intake [6].
• Influence of grenz rays and psychological factors on experimental pruritus induced by histamine and compound 48/80 [7].

High impact information on p-Methoxy-N-methylphenethylamine

• Mast cell depletion using compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was shown histologically to induce mast cell degranulation [8].
• In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity [9].
• In line with this, we found that PLCbeta3(-/-) mice showed significant defects in scratching behavior induced by histamine; histamine-trifluoromethyl-toluidine (HTMT), a selective H1 agonist; and compound 48/80, a mast cell activator [10].
• Ca2+-dependent acylhydrolase activity and PGE2 production were inhibited by calmodulin inhibitors, W-7 and compound 48/80 [11].
• Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying [12].

Chemical compound and disease context of p-Methoxy-N-methylphenethylamine

• Increased compound 48/80 induced local histamine release from nonlesional skin of patients with chronic urticaria [13].
• Pretreatment of mast cells with pertussis toxin decreased the secretagogic effect of LysoPS and compound 48/80 without modifying the effect of the ionophore A23187 [14].
• Amitriptyline also blocked paw edema produced by 5-hydroxytryptamine and compound 48/80 [15].
• NGF injection caused edema which was absent in rats pretreated with compound 48/80 as well as in rats treated neonatally with capsaicin ('capsaicin denervation') [16].
• Prostaglandin D2 release by guinea pig skin during in vitro anaphylaxis induced by antigen and compound 48/80 [17].

Biological context of p-Methoxy-N-methylphenethylamine

• Calmidazolium and compound 48/80 inhibit calmodulin-dependent protein phosphorylation and ATP-dependent Ca2+ uptake but not Ca2+-ATPase activity in skeletal muscle sarcoplasmic reticulum [18].
• No similar binding sites have been identified in peripheral tissue preparations, and other polycationic mast cell-degranulating agents including compound 48/80 show no such specificity [19].
• Compound 48/80-induced secretion is associated with transient hydrolysis of phosphoinositides and a transient increase in cytosolic calcium ions [20].
• We used intravital microscopy to visualize leukocyte-rolling flux and adhesion in single 25 to 40 microns venules in mesenteric preparations that were treated with the mast cell-degranulating agent, compound 48/80 (CMP 48/80) [21].
• At optimal stimulation with 10 micrograms/ml compound 48/80 secretion is inhibited with an IC50 = 50 microM and a Hill coefficient n = 10 [22].

Anatomical context of p-Methoxy-N-methylphenethylamine

• Compound 48/80-activated mast cells evoked a significant increase in PAF-dependent neutrophil adhesion in vitro [23].
• [3H]Galactose, covalently bound to cell surface glycoconjugates of rat peritoneal mast cells, was used to study internalization of labeled plasma membrane and granule membrane constituents before or after secretion stimulated by compound 48/80 [24].
• Intravital fluorescence microscopy was used to demonstrate increased leukocyte rolling and adhesion and increased albumin extravasation in single 25- to 40-microns venules that were treated with the mast cell-degranulating agent compound 48/80 (CMP 48/80) [23].
• Stimulation of the mast cells with compound 48/80, a degranulating agent, resulted in dose-dependent release of secretory granules from the mast cells and a parallel increase in cholesteryl ester synthesis in the macrophages [25].
• Diphenhydramine also caused a significant delay in the response to compound 48/80 in normal guinea pig trachea and to antigen in actively sensitized trachea, indicating that the antihistamine was capable of inhibiting tracheal contractions to endogenously released histamine [26].

Associations of p-Methoxy-N-methylphenethylamine with other chemical compounds

• Here we have examined changes in the organization of actin filaments in intact mast cells after activation by compound 48/80, and in permeabilized cells after direct activation of GTP-binding proteins by GTP-gamma-S [27].
• These HF-derived leukocytes showed characteristic features of connective tissue-type mast cells, including proliferative responsiveness to SCF, metachromatic granules, mRNA expression for mast cell proteases-1, -4, -5, and -6, and histamine release on ligation of surface IgE or stimulation with substance P or compound 48/80 [28].
• Proliferative potential of murine peritoneal mast cells after degranulation induced by compound 48/80, substance P, tetradecanoylphorbol acetate, or calcium ionophore A23187 [29].
• Results indicated that in vivo treatment with TGF-beta 1 24 h before mast cell harvest inhibited the in vitro release of serotonin in response to challenge with compound 48/80, or anti-IgE antibody [30].
• The increase in leukocyte adherence was not affected by pretreatment with a mast cell stabilizer (sodium cromoglycate) nor by prior degranulation of mast cells with compound 48/80 [31].

Gene context of p-Methoxy-N-methylphenethylamine

• The effect of CRH on Evans blue extravasation was stronger than equimolar concentrations of the mast cell secretagogue compound 48/80 or SP [32].
• Moreover, systemic administration of antalarmin, a nonpeptide CRHR1 antagonist, prevented vascular permeability only by CRH and not by compound 48/80 or SP [32].
• Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice [33].
• 5. The substance P analogue, [D-Pro4,D-Trp7,9,10] SP4-11 (SPA), not only reduced substance P-induced histamine release in a concentration-related manner but also inhibited that induced by VIP, somatostatin, compound 48/80, poly-L-lysine and morphine but not anti-IgE [34].
• We now demonstrate that pertussis toxin (Ptx)-sensitive Gi proteins, activated by compound 48/80 (c48/80), a potent member of this family, also activate the p42/p44 MAP kinases (MAPKs) [35].

Analytical, diagnostic and therapeutic context of p-Methoxy-N-methylphenethylamine

• In contrast, the intradermal injection of 5 micrograms of compound 48/80 produced a significant increase in plasma histamine [36].
• After 1 wk in coculture, RBL-2H3 cells began to respond to compound 48/80 [37].
• In addition, compound 48/80 showed a negligible effect on the circular dichroism spectrum of the mutant [38].
• Uptake of material from surrounding medium by activated rat peritoneal mast cells (PMCs) was studied using in vitro peritoneal eluate cells, the vital fluorescent dye sulforhodamine B (SFRM-B), secretagogue compound 48/80, and an imaging technique [39].
• Histologic studies of human skin test responses to ragweed and compound 48/80. II. Effects of corticosteroid therapy [40].

References