THE ROLE OF HISTAMINE Hr AND H2‐RECEPTORS IN THE GENERATION OF THROMBOXANE A2 IN PERFUSED GUINEA‐PIG LUNGS

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Abstract
1 When isolated perfused lungs from normal and ovalbumin sensitized guinea-pigs were challenged with histamine and 2-methylhistamine (agonists for Hj-receptor), a release of thromboxane A2-like substance was observed. The effect of histamine on production of thromboxane A2 (TXA2) in sensitized lungs, was more pronounced than in normal lungs (P < 0.01). 2 Specific activation of histamine H2-receptors in normal lungs with large doses (100 jag) of dimaprit and 4-methylhistamine, does not produce thromboxane-like or prostaglandin-like substances. 3 Perfusion of the lungs with pyrilamine (10 μg/ml) inhibited the release of arachidonate metabolites induced by histamine H1-receptor stimulation, whereas cimetidine (5 μg/ml) was ineffective. 4 It is concluded that only the stimulation of histamine H1-receptors appears to be responsible for generation of thromboxane A2 and other prostaglandin-like substances in normal guinea-pig lungs. In sensitized lungs, an increased ability of histamine to release TXA2 could be due to a possible interconversion of H2 into Hj-receptors.