Abstract
Slow reacting substance (SRS) is a smooth muscle-contracting activity released from lung and other tissues. Because of its physiological effect and immunologic origin, it was thought that SRS might play an important role as a mediator of immediate hypersensitivity reactions in asthma and other symptoms. Immunologically generated SRS was named slow reacting substance of anaphylaxis (SRS-A). Recently, SRS-A was identified as the mixture of substances derived from arachidonic acid and named leukotrienes C and D (LTC and LTD). The present investigation was conducted to explore the effect of synthetic LTC4 and LTD4 on the isolated guinea pig tracheal strips.
Male Hartley strain guinea pigs, weighing 200-250g, were sacrificed. Guinea pig tracheal strips were removed and suspended in bioassay glass jackets and superfused with Krebs-Henseleit solution at 37°C, saturated with oxygen and carbon dioxide (95:5, V/V). Contraction of tissues was detected by an isotonic transducer and displayed on a polyrecorder.
1) LTC4 and LTD4-induced contractile responses and their duration were greater than those induced by histamine.
2) LTC4 and LTD4 elicited the contractile responses in guinea pig tracheal strips dose-dependently. LTD4-induced contractile response was almost 10 times greater than that induced by LTC4.
3) Acetylcholine-, histamine-, serotonin- and prostaglandin F2α-induced contractile responses were markedly potentiated by continuous infusion of LTC4 and LTD4.
4) LTD4- and LTC4-induced contractile responses were markedly potentiated by continuous infusion of indomethacin, and they reached maximum at the dose of 5×10-7M of indomethacin.
The above results suggest that LTC4- and LTD4-induced response are not mediated by prostaglandins and that they may play an important role in pathological conditions such as bronchial asthma or anaphylactic shock.
