sq-23377 and doxantrazole

Cyclic AMP analogues and the anti-allergic drugs disodium cromoglycate, quercetin, doxantrazole and theophylline inhibited histamine secretion from rat peritoneal mast cells stimulated with the calcium ionophore ionomycin. The potency of the compounds varied inversely with the concentration of ionophore and with the period of incubation. The drugs were active in both the presence and absence of extracellular calcium. These results cannot be explained in terms of the postulated effect of the compounds on the receptor-mediated activation of calcium-channels. Alternative mechanisms for their action are thus considered.

Topics: Animals; Bronchodilator Agents; Calcium; Cromolyn Sodium; Cyclic AMP; Ethers; Female; Histamine H1 Antagonists; Histamine Release; Ionomycin; Ionophores; Kinetics; Male; Mast Cells; Quercetin; Rats; Rats, Inbred Strains; Theophylline; Thioxanthenes; Xanthones

Functional mast cells have been isolated from the lamina propria of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells released histamine on challenge with specific antigen, anti-rat IgE, concanavalin A, and calcium ionophores but were less responsive than peritoneal mast cells (MMC) from the same animals. Intestinal mucosa mast cells (PMC) were refractory to the action of the basic secretagogues peptide 401 from bee venom and compound 48/80. The anti-allergic compounds disodium cromoglycate (less than or equal to 10(-3) M), AH 9679 (less than or equal to 10(-4) M), and theophylline (less than or equal to 10(-2)) did not inhibit antigen-induced histamine secretion by MMC, although these compounds were effective against PMC. In contrast, doxantrazole (10(-5) to 10(-3) M) inhibited the secretion of histamine from both MMC and PMC in a comparable dose-dependent fashion. Thus, we have established that mast cells from different sites are functionally heterogeneous not only in their response to various stimuli for histamine secretion, but also in their responses to different pharmacologic modulators of secretion. It cannot be assumed that anti-allergic compounds effective against mast cells in one tissue site or organ will be equally efficacious against mast cells in other sites. The extent of this functional heterogeneity must be established, and its investigation may provide new insights into the biochemical events involved in mast cell secretion.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Ascitic Fluid; Calcimycin; Cell Separation; Cromolyn Sodium; Ethers; Histamine Release; Hookworm Infections; Intestinal Mucosa; Ionomycin; Mast Cells; p-Methoxy-N-methylphenethylamine; Rats; Rats, Inbred WF; Theophylline; Thioxanthenes; Xanthones