Prostaglandin Production by Rabbit Isolated Jejunum and Its Relationship to the Inherent Tone of the Preparation

Abstract

I Pieces of rabbit jejunum were bathed in Krebs solution at 37°C in an isolated organ bath bubbled with 02 and 5% CO2. The bathing fluid was collected regularly and assayed for prostaglandins. 2 The preparations maintained a continuous sub-maximal muscle contraction, referred to as inherent 'tone'. Prostaglandins E2 and FM were continuously generated by the intestine and released into the bathing fluid. The amounts released first declined over 2 h and then steadily increased. The release was also greater after 48 h storage in the refrigerator and after mechanical damage. 3 There was no change in prostaglandin release when the rabbit jejunum was contracted by acetylcholine or physostigmine or relaxed by adrenaline, hyoscine, papaverine, dinitrophenol, or calcium-free Krebs solution. 4 Addition to the bathing fluid of the prostaglandin precursor, arachidonic acid, did not increase the release of prostaglandins although it contracted the tissue. Thus, output of prostaglandins from the tissue was not limited by substrate concentration but more probably by the capacity of the prostaglandin synthetase. 5Prostaglandin output was decreased by bubbling the bathing fluid with N2 rather than 02; at the same time the preparation relaxed. 6 Aspirin-like drugs such as indomethacin also decreased or abolished prostaglandin formation and this, too, was accompanied by loss of tone of the isolated preparation. 7 Pieces of rabbit jejunum stored in Krebs solution containing indomethacin initially released little or no prostaglandin into the bathing fluid. However, prostaglandin release increased with repeated washing of the preparation. 8 The results suggest that intra-mural prostaglandin production contributes to the inherent tone of the rabbit jejunum, that trauma increases prostaglandin production and that the inhibitory effects of anoxia are linked with the lack of prostaglandin production and activity. The relevance of these findings to intestinal activity in vivo is discussed.

The Effects of Non‐steroidal Anti‐inflammatory Drugs on Cholinergic and Histamine‐induced Contractions of Guinea‐pig Isolated Ileum

“…Prostaglandins seem to play a role in contractions of intestinal smooth muscle (Bergstr6m, Eliasson, Von Euler & Sjoval, 1959;Bennett, Eley & Scholes, 1968;Fleshler & Bennett, 1969;Eckenfels & Vane, 1972;Ferreira, Herman & Vane, 1976). Since the demonstration that indomethacin inhibits prostaglandin synthesis in cell-free homogenates of guineapig lung (Vane, 1971), many authors have confirmed the inhibitory action of non-steroidal antiinflammatory drugs (NSAID) on prostaglandin synthesis in various tissues (Flower, 1974).…”

Spontaneous Tone in Different Types of Longitudinal Muscle Preparations of Guinea Pig Ileum

“…Indomethacin inhibited the tone by approximately a half. In the rabbit small intestine, prostaglandins such as the E series were suggested to be the main substance responsible for the inherent tone, accounting for about 70-80% (6). Although the contribution of prostaglandins in the guinea pig ileum does not seem to be as large as that in the rabbit ileum, it is likely that prostaglandins may play a role in sustaining the tone either by itself or in concert with the neural mechanisms.…”

“…It has been suggested that neurogenic (1)(2)(3) and myogenic mechanisms (4) are responsible for these activities. Autacoids such as prostaglandins, in addition, may also be involved in maintaining tone (5,6).…”

Involvement of Thromboxane A2in the Modulation of Pacemaker Activity of Interstitial Cells of Cajal of Mouse Intestine

“…Both the mucosa and the muscle layer of the gut are capable of generating the major products of biotransformation of arachidonic acid via the cyclooxygenase pathway such as PGE2, PGF2α, PGI2, and thromboxanes (Bennet et al, 1968;Ferreira et al, 1976;LeDuc & Needdleman, 1979;Robert, 1981;Sanders, 1981;Sanders, 1984). Among the rest, thromboxane A2 (TXA2) is well known to alter the GI activity.…”