HISTAMINE FORMING CAPACITY (HFC) AND ITS MODULATION BY H-3 RECEPTOR LIGANDS IN A MODEL OF BRONCHIAL HYPERRESPONSIVENESS

The histamine forming capacity (HFC) of acutely challenged airways fro m sensitised guinea pigs was investigated. After exposure to nebulised bovine serum albumin (BSA) or normal saline, animals were sacrificed, the pulmonary HFC determined and concurrent in vitro histamine log co ncentration response curves were constructed for parenchymal strips an d tracheal muscle, the latter was field stimulated to record neurogeni c responses. Exposure to BSA increased the HFC above controls for 24 h ours (p < 0.001) and log concentration response curves for the parench ymal strips were shifted slightly to the left with an increased maximu m response. This change appeared 3 hours after exposure and remained e levated at 14 hours. Similar changes did not occur with the trachea. P re-treatment with thioperamide augmented (p < 0.02) HFC and this incre ase was inhibited by alpha-methylhistamine (p < 0.05). A possible rela tionship may exist between increased responsiveness of lower airways t o exogenous histamine and a raised endogenous formation, regulated by the H-3 receptor.