[CITATION][C] Comparative contractile responses to sulfidopeptide leukotrienes in normal and asthmatic human subjects

JM Drazen - Annals of the New York Academy of Sciences, 1988 - Wiley Online Library
Annals of the New York Academy of Sciences, 1988Wiley Online Library
The sulfidopeptide leukotrienes-LTC,, LTD,, and LTE,-are all known to become available in
the cellular microenvironment after a variety of challenge^.'-^ This includes physiological
stimuli, such as as well as distinctly nonphysiological stimuli, such as the calcium ionophore
A23 1 87.6. 7 Under some circumstances, it also is clearly established that only LTC, is
produced as the primary cellular product and that the metabolic conversion associated with
alteration of the peptide side chain occurs as a result of events separate from those that …
The sulfidopeptide leukotrienes-LTC,, LTD,, and LTE,-are all known to become available in the cellular microenvironment after a variety of challenge^.'-^ This includes physiological stimuli, such as as well as distinctly nonphysiological stimuli, such as the calcium ionophore A23 1 87.6. 7 Under some circumstances, it also is clearly established that only LTC, is produced as the primary cellular product and that the metabolic conversion associated with alteration of the peptide side chain occurs as a result of events separate from those that initiate leukotriene synthesis. For example, when eosinophils are the target cell and A23 187 is the initiating stimulus, only LTC, is produced. 8 In guinea pig pulmonary parenchymal strips, exposure to the chemotactic peptide, formyl-methionyl-leucyl-phenylalanine, results in the synthesis of LTC,; other sulfidopeptide leukotrienes are not originally produced.'However, it is well established that incubation of LTC, with lung parenchymal tissues is associated with the bioconversion of LTC, to LTD, and LTE,." Thus, in the lung, even if only LTC, is produced, all three sulfidopeptide leukotrienes are likely to be bioavailable. A major action of these compounds on airways is to initiate a contractile response."-" Evidence obtained from studies of guinea pig tissues suggests that there are distinct contractile receptors for LTC, and LTD,"*'4 and that there may even be a distinct receptor for LTE4. I5 In contrast, studies of isolated human 2-4-mm airways (obtained at the time of surgery for carcinoma of the bronchus) suggest that these airways contain only a single contractile receptor for LTC, and LTD4. I6 Because this latter evidence was obtained only with a single anatomical class of airways (the so-called medium-sized airways), it is possible that a broader survey of airway tissues could have revealed systematic differences among tissues in their sulfidopeptide leukotriene receptor complement. We reasoned that examination of the airway responses of normal and asthmatic humans to aerosols generated from solutions of each of the sulfidopeptide leukotrienes could yield insights into the comparative potency and sites of response of each of these compounds.
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