Histamine forming capacity (HFC) and its modulation by H3 receptor ligands in a model of bronchial hyper-responsiveness.
The histamine forming capacity (HFC) of acutely challenged airways from 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 concentration response curves were constructed for parenchymal strips and tracheal muscle, the latter was field stimulated to record neurogenic responses. Exposure to BSA increased the HFC above controls for 24 hours (p < 0.001) and log concentration response curves for the parenchymal strips were shifted slightly to the left with an increased maximum response. This change appeared 3 hours after exposure and remained elevated at 24 hours. Similar changes did not occur with the trachea. Pre-treatment with thioperamide augmented (p < 0.02) HFC and this increase was inhibited by alpha-methylhistamine (p < 0.05). A possible relationship may exist between increased responsiveness of lower airways to exogenous histamine and a raised endogenous formation, regulated by the H3 receptor.
Allen
M C
MC
John Harris Clinical Pharmacy Unit, University of Brighton, UK.
Graham
P
P
Morris
G
G
D000818:Animals; D001665:Binding Sites; D016535:Bronchial Hyperreactivity / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000096:biosynthesis* / Q000378:metabolism; D017442:Histamine Agonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008024:Ligands; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008761:Methylhistamines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000633:toxicity; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D017442:Histamine Agonists; D006633:Histamine Antagonists; D008024:Ligands; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; D012710:Serum Albumin, Bovine; C069357:alpha-methylhistamine; D006632:Histamine; C052075:thioperamide