Immunologic release of histamine from dog lung: comparison of in vivo and in vitro responses in the same animal.
The purpose of this study was to compare, for the first time, antigen-induced histamine release from the lung in the same natively allergic dogs both in vitro and in vivo. In six dogs, maximal antigen-induced histamine release from the lung correlated closely in vitro and in vivo (r = 0.94), although it varied widely between dogs (0% to 75.5% of total tissue histamine content); similarly, the antigen concentration to produce 50% of maximal histamine release varied sixfold between dogs (40 micrograms/ml to 250 micrograms/ml). In each of five other dogs, terbutaline sulfate administered intravenously caused a dose-dependent inhibition of antigen-induced histamine release from lung fragments in vitro: the maximal inhibition produced by 1 mg/kg was 60 +/- 4.5% (mean +/- SEM). In these same dogs, 10(-5)M terbutaline incubated with lung fragments in vitro caused inhibition of antigen-induced histamine release comparable to 1 mg/kg terbutaline in vivo. Increasing the dose of terbutaline in vitro produced maximal inhibition at 10(-4)M with no greater effect of the drug at 10(-3)M (71.4 +/- 3.8% inhibition). In both experimental situations propranolol caused a dose-dependent inhibition of beta-adrenergic modulation of Ascaris-induced release of histamine. This result supports the conclusion that terbutaline produced its effects by actions mediated by beta-adrenergic receptors on pulmonary mast cells. This experimental approach provides a suitable preparation in which to estimate the effective dose of agonists that modulate antigen-induced mast cell function in vivo.
D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D006632:Histamine / Q000276:immunology*; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology*; D013726:Terbutaline / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000947:Antigens, Helminth; D006632:Histamine; D007545:Isoproterenol; D013726:Terbutaline