Release of rabbit aorta contracting substance (RCS) and prostaglandins induced by chemical or mechanical stimulation of guinea‐pig lungs

Abstract

Summary1. Rabbit aorta contracting substance (RCS) and prostaglandins were released from guinea-pig isolated perfused lungs by gentle massage and also by infusion of Prosparol.2. RCS and prostaglandins were also released by infusion into the pulmonary artery of bradykinin, arachidonic and dihomo-'y-linolenic acids or shock perfusate (containing RCS-releasing factor).3. Arachidonic and dihomo-y-linolenic acids caused a prolonged release of RCS and prostaglandins whereas bradykinin and shock perfusate gave a short-lasting output. 4. RCS and prostaglandins, together with histamine were released when superfused chopped lung tissue was agitated. 5. Challenge of sensitized guinea-pigs in vivo led to the release of an RCSlike substance into the carotid arterial blood. 6. Intravenous injection of bradykinin into guinea-pigs also released an RCSlike substance. 7. The release of RCS and prostaglandins was inhibited by aspirin or indomethacin in all experiments. 8. RCS contracted all vascular tissues investigated and also rat stomach strip. 9. The half-life of RCS was estimated as 1-2 minutes.

Studies on the Action Potential Originated From Nerve Elements in Guinea Pig Ureter

“…These findings indicate that the aspirin-like drugs antagonize the arachidonic acid-induced contraction of the rat fundus through inhibiting formation of the endoperoxides from arachidonic acid. Therefore, the highly significant correlation released from the lung, and that aspirin, which inhibits their release, also antagonizes the bradykinin-induced bronchoconstriction (19). The activity of RCS is now thought to be due mainly to thromboxane A2 (TXA2), which is produced from the endoperoxides PGG2…”

PHOSPHOLIPASE A2 ACTIVITY OF GUINEA‐PIG ISOLATED PERFUSED LUNGS: STIMULATION, AND INHIBITION BY ANTI‐INFLAMMATORY STEROIDS

“…For example, when arachidonic acid is infused into guinea-pig isolated perfused lungs it is immediately converted to RCS (Vargaftig & Dao Hai, 1972;Palmer et al, 1973); that this really is a conversion not a release is easily demonstrated with labelled arachidonate. This suggests that in this system at least, substrate availability is the rate limiting reaction.…”

“…The list includes histamine (Piper & Vane, 1969;Bakhle & Smith, 1972;Liebig, Bernhauer & Peskar, 1974), bradykinin (Piper & Vane, 1969;Vargaftig & Dao Hai, 1972), 5-hydroxytryptamine (Alabaster & Bakhle, 1970;1976), and rabbit aorta contracting substancereleasing factor (RCS-RF) (Piper & Vane, 1969;Nijkamp, Flower, Moncada & Vane, 1976) as well as mechanical trauma or antigen challenge (Piper & Vane, 1969;1971;Palmer, Piper & Vane, 1973;Liebig et al, 1974). Injection or infusion of the precursor arachidonic acid into the preparation also leads to the generation of prostaglandin endoperoxides and TXA2, (Vargaftig & Dao Hai, 1972;Palmer et al, 1973;Hamberg & Samuelsson, 1974) and it has therefore been inferred that 'substrate availability' is an important rate-limiting step in this reaction, and that agents which release these fatty acid derivatives do so by liberating the substrate from some endogenous lipid pool. The arachidonate content of most cells is high but little arachidonic acid is present in the 'free' form (Kunze & Vogt, 1971;Samuelsson, 1972;Haye, ' Present address: Rudolf Magnus Institute for Pharmacology, Vondellaan 6, Utrecht, The Netherlands.…”

Release of Mediators of Anaphylaxis: Inhibition of Prostaglandin Synthesis and the Modification of Release of Slow Reacting Substance of Anaphylaxis and Histamine

“…When injected or infused into guinea-pig perfused lungs, histamine and SRS-A release rabbit aorta contracting substance (RCS) (a mixture of thromboxane A2 and endoperoxides) and prostaglandin-like material (Palmer et al, 1973;Liebig et al, 1975;Engineer et al, 1976;Engineer et al, unpublished results) so that endoperoxides, thromboxanes, prostacyclin or prostaglandins released in anaphylaxis may influence further release of SRS-A and histamine, perhaps through an interaction with cyclic nucleotides. Further investigation is required to establish the relative importance of individual products of arachidonic acid metabolism.…”

“…Also Tauber et al (1973) have shown that low concentrations of prostaglandin E1 and F2a depressed cyclic adenosine 3',5'-monophosphate (cyclic AMP) levels in human chopped lung and enhanced mediator release. Since the percentage conversion of arachidonic acid to prostaglandins in perfused lungs is very low (approximately 0.1%; calculated from Palmer et al, 1973), the concentration of prostaglandins formed might have lowered the cyclic AMP levels.…”