Abstract
Prostaglandins are synthesized by a multienzyme complex referred to loosely as PG synthetase. This enzyme complex appears to be present in every mammalian tissue and organ including the lung.
The present investigation was conducted to study the effect of various drugs on the biosynthesis of prostaglandin-like substances (PGLS) from arachidonic acid (A.A) through isolated perfused guinea pig lung lobes.
Male guinea pigs, weighing 250-300g, were used. Heart and lungs were removed and the lower half of the heart was cut away. The lungs were then suspended in a bioassay glass chamber and perfused through the pulmonary vein with Krebs-Henseleit solution containing 25% fluosol-43 at 37°C saturated with oxygen and carbon dioxide (95:5, v/v). The rate of perfusion was constant at 10ml/min. For the detection of PGLS the effluent from the lungs was superfused over assay tissues; these were rat colons (R.C.).
Contraction of rat colons was detected by an isotonic transducer and displayed on a polyrecorder. Arachidonic acid was infused into the pulmonary vein and PGLS activity synthesized from A.A was assayed.
1) Per cent conversion from A.A. to PGLS was decreased by increasing the dose of A.A.
2) Per cent inhibition of PGLS synthesis from A.A. with indomethacin and aspirin increased dose-dependently, and per cent inhibition with indomethacin was greater than with aspirin.
3) Per cent conversion from A.A to PGLS increased markedly by combination with histamine, serotonin, bradykinin and adrenaline, and per cent conversion increased dose-dependently.
4) Above results suggest that these chemical mediators may correlate with inflammatory and allergic responses not only by direct action but also by indirect action resulting from acceleration of PGLS synthesis.
