An improved method for the study of reagin-mediated mast cell degranulation in rats

Inhibition of Antigen-Induced Histamine Release by β-Adrenergic Stimulants <i>in vivo</i>

“…The present work is supported by in vivo results showing modification by /3-stimu lants of the antigen-induced mast cell de granulation [10,11]. Correlation may, how ever, be complicated as there are two com patible processes through which mast cells may degranulate, both exocytosis and pore formation being considered significant mechanisms [42], Differentiation of Drug Action PPA was used as a method of comparing in the same animals both inhibition of his tamine release and dye extravasation, the latter measure representing the total action on the cellular and the vascular level.…”

“…It is true that /5-stimulants have a definite effect on skin reactions, e.g., reagin-mediated passive cutaneous anaphy laxis in the rat [1,11,23], human immedi ate hypersensitivity skin reactions [25,37,38] and allergic rhinitis [17], It is not clear, however, whether this in vivo protection is brought about at the level of mediator re lease from the mast cells or on the level of the small blood vessels, or both. Evidence suggests that /5-stimulants have a direct action on the vascular system itself [2,13,32,43]; mediators may cause intercellular gaps by contraction of endothelial cells [22], and relaxation of the cells might be the mecha nism for the inhibitory effect of /5-stimulants [41]Unlike the situation with the 'over-all' assessment of anaphylaxis mentioned above (without discriminating between cellular and vascular effects), there are to our knowledge only very few in vivo investigations which substantiate the specific anti-anaphylactic component in question: the inhibiting effect of two ^»-receptor stimulants, fenoterol and salbutamol, on antigen-induced [10,11] and dextran-induced [11] mast cell degranula tion has been demonstrated. Similar results are available with aminophylline [33], which inhibits breakdown of cAMP.…”

Synthesis and structure-activity relations of 5H,11H-[2]benzopyrano[4,3-g][1]benzopyran-9-carboxylic acids

“…The crude product on recrystallization provided lw as yellow needles (see Table I). l,3-Dimethoxy-2-acetyl-6,6-dimethyl-677-dibenzo [6,d]pyran (8). A solution of lw (100 mg) in 1 N NaOH (10 ml) was heated under reflux for 20 min.…”

“…The reaction mixture was poured into 30% NaHS03 solution (25 ml) and the crude product collected by filtration. Recrystallization from EtOH provided 9a (0.15 g, 52%) as yellow needles: mp 286-300 °C dec; NMR (CD3SOCD3) 1.63 [s, 6 H, (CH3)2], 6.48 (s, 1 H, C-3-H), 7.00 (s, 1 H, C-6-H), 7.43 (m, 3 H, C-9 + C-10 + C-ll), 8.60 (m, 1 H, C-12-H), 12.43…”

“…The constitution (lw) was assigned on the basis of spectral information and was confirmed by the following degradation. Alkaline hydrolysis of the demethylated product yielded the corresponding acetophenone which was methylated to a dimethyl ether, identical in all respects with l,3-dimethoxy-2-acetyl-6,6-dimethyl-6fl-dibenzo[i>,d]pyran12 (8). The transformation (5 -*• lw) undoubtably involved the initial formation of the hydroxy acid 6 which subsequently provided the carbonium ion 7 which rearranged and ring closed to the more favorable form (lw).…”