Mediation of prostaglandin E2 in the triphasic response to ATP of the isolated tracheal muscle of guinea-pigs

Abstract

ATP, at a dose higher than 0-1 mug m1(-1), showed a biphasic action consisting of an initial increase followed by a gradual decrease of muscle tension in the isolated tracheal strip-chains of guinea-pigs. The pattern of this biphasic response to ATP varied with the level of basal tone of the preparation at the moment of application of ATP. A smiliar biphasic action was obtained by prostaglandin (PG) E2 among the various active substances studied including acetylcholine, histamine, catecholamines and various types of PG. Indomethacin (0-1 mug m1(-1) and aspirin (30 mug m1(-1)) completely abolished the ATP-induced inhibitory response observed in the presence of histamine (10 muM). Polyphloretin phosphate (100 mug m1(-1)) also significantly depressed the inhibitory response to ATP or PGE2. It is concluded that the response to ATP of the preparation is mediated by PGE2 released via the stimulation of its biosynthesis.

The effect of adenyl compounds on the rat heart

“…APPCP and APCPP) are unable to stimulate prostaglandin synthesis, unlike ATP (Brown & Burnstock, 1981). Responses to ATP have been found to be mediated either partly or wholly by prostaglandins in a number of preparations (Burnstock, Cocks, Paddle & Staszewska-Barczak, 1975;Kamikawa & Shimo, 1976;Brown & Burnstock, 1981). However, the effects of ATP in the rat ventricle do not appear to be mediated via prostaglandins since indomethacin, a prostaglandin synthetase inhibitor (Vane, 1971), failed to antagonize them.…”

Dual effect of (−)‐N6‐phenylisopropyl adenosine on guinea‐pig trachea

“…Evidence for a purinergic inhibitory innervation of the guinea-pig and dog trachea has been obtained by several groups in recent years (Cobum & Tomita, 1973;Coleman & Levy, 1974; Richardson & Bouchard, 1975;Coleman, 1976;Farmer & Farrar, 1976;Kamikawa & Shimo, 1976;Cameron & Kirkpatrick, 1977;Christie & Satchell, 1980;Satchell & Maguire, 1983). Most of the research in this field deals with the ability of adenosine to relax airway smooth muscle.…”

“…Most of the research in this field deals with the ability of adenosine to relax airway smooth muscle. However, excitatory responses to ATP and adenosine have been observed (Coleman & Levy, 1974;Kamikawa & Shimo, 1976;Coleman, 1976).…”

Influence of resting tension on protease-activated receptor-mediated relaxation in guinea-pig tracheas

“…precontracted with histamine [10] and ACh [11] in a COXdependent manner. Moreover, in agreement with the functional experiments the direct quantification of PGE 2 production demonstrates that ATP is able to increase PGE 2 release at both resting tensions tested.…”

“…Old data obtained in guinea-pig tracheal strips [10], demonstrate that PGE 2 as well as ATP are contractile agonists at low resting tone, but relaxing agents when the resting tension is set at high values and when the tension is increased by histamine pre-treatment. Similar results are also described by Advenier and co-authors [11] regarding the effect of ATP and adenosine on guinea-pig tracheas.…”