Prostaglandins, oxygen tension and smooth muscle tone

Self Cite

190

Summary1. Indomethacin and meclofenamate, both of which are potent inhibitors of prostaglandin synthetase, antagonized the contractor effects of oxytocin on the isolated uterus from the non-pregnant rat. Contractions induced by acetylcholine or prostaglandin F2a were not antagonized.2. Uteri from rats 17-22 days pregnant exhibited intermittent spontaneous contractions when used as isolated preparations. They also released prostaglandin-like activity (mainly similar to F2a) into the bathing fluid. Both the prostaglandin release and the uterine activity were abolished by indomethacin. Activity could be restored by addition of low concentrations of prostaglandin E2 or F2a.3. The release of prostaglandin F2a-like activity by the uteri increased dramatically on the expected day of delivery (day 22). 4. The results add force to the hypothesis that the spontaneous activity of some isolated organs is due to an intramural prostaglandin generation, and that increased uterine prostaglandin production contributes to the expulsion of the foetus.

Section: Discussionmentioning

confidence: 99%

The contribution of prostaglandin production to contractions of the isolated uterus of the rat

Vane

Williams

1973

Self Cite

190

“…Several investigators have previously suggested that endogenous prostaglandins play an important role in the maintenance of tone and the development of spontaneous contractility in the mammalian bladder (Eckenfels & Vane, 1972;Bultitude et al, 1976; domethacin, aspirin and corticosterone. In addition, the cyclo-oxygenase inhibitors also reduced the response to phentolamine in a concentrationdependent manner.…”

Section: Discussionmentioning

confidence: 99%

Phentolamine‐induced rhythmic contractions in bladder detrusor muscle of guinea‐pig

Satake¹,

Shibata²,

Ueda³

1984

1 Phentolamine caused a rhythmic contraction concentration-dependently without affecting resting tone in the detrusor muscle.2 Prazosin, yohimbine, propranolol, noradrenaline, clonidine or isoprenaline failed to cause the rhythmic contraction. These agents did not modify the response to phentolamine suggesting no involvement of a-or , -adrenoceptors in the response to phentolamine. 3 Chlorpheniramine, cimetidine, methysergide, SK&F 83566, atropine, bretylium, hemicholinium or tetrodotoxin failed to inhibit the response to phentolamine. These results suggest that the effect of phentolamine is not mediated through histaminergic, 5-hydroxytryptaminergic, dopaminergic or cholinergic systems, or through transmitter release from nerve endings.4 Prostaglandin F2, (PGF2,), arachidonic acid but not ATP caused rhythmic contractions which resembled the response to phentolamine. Potassium also caused a contraction with increasing resting tone.5 Following treatment with nifedipine, or incubation in a Ca22-free medium, the responses to phentolamine, PGF2a, arachidonic acid and potassium were markedly inhibited or abolished. 6 Cyclo-oxygenase inhibitors such as indomethacin, aspirin and corticosterone inhibited or abolished the responses to phentolamine and arachidonic acid but did not inhibit the response to PGF2,. 7 The results suggest that the phentolamine-induced rhythmic contraction may, at least in part, result from the cyclo-oxygenase metabolite of arachidonic acid in guinea-pig detrusor muscles and a consequent increase in the transmembrane Ca2 + -influx.

“…The abolition of these changes by incubation with indomethacin suggests that the strips of gall bladder release a prostaglandin-like substance, which in turn affects the tonic and phasic activity of the muscle. other guinea-pig isolated tissues (ileum, Davison et al, 1972;Botting & Salzmann, 1975;trachea, Orehek et al, 1975;taenia coli, Sakato & Shimo, 1976), rabbit jejunum (Ferreira, Herman & Vane, 1972), rat stomach strip and chick rectum (Eckenfels & Vane, 1972). Although a noradrenergic innervation to the guinea-pig gall bladder has been clearly demonstrated (Baumgarten & Lange, 1969;Davison et al, 1978), there have been few studies of the effects of exogenously applied catecholamines on this tissue.…”

Section: Discussionmentioning

confidence: 99%

THE EFFECTS OF TIME AND INDOMETHACIN ON CONTRACTILE RESPONSES OF THE GUINEA‐PIG GALL BLADDER in vitro

Doggrell

Scott

1980

The effects of time and of indomethacin on contractile responses of the guinea‐pig gall bladder were studied in vitro. The tissues contracted to field stimulation at 5 Hz (in the absence and presence of atropine 10−6 m), (‐)‐noradrenaline (10−5 m), acetylcholine (10−5 m), and adenosine 5′‐triphosphate (ATP, 10−4 m); the magnitude of the contractile responses increased with time. (‐)‐Isoprenaline 10−5 m either relaxed (17 of 23 preparations tested) or had no effect on gall bladder strips. The responses of strips of guinea‐pig gall bladder to field stimulation at 5 Hz (in the absence or presence of atropine 10−6 m), (‐)‐noradrenaline (10−5 m), and acetylcholine (10−5 m) obtained 4 h 45 min after setting up the tissue were reduced following incubation with indomethacin (7.9 times 10−6 m for 1 h). The responses to (‐)‐isoprenaline (10−5 m) and to ATP (10−4 m) were abolished by incubation with indomethacin. These results suggest that, in the guinea‐pig gall bladder in vitro, the magnitude of the contractile responses to field stimulation at 5 Hz, (‐)‐noradrenaline (10−5 m), and acetylcholine (10−5 m) and the ability of the tissue to respond to (‐)‐isoprenaline (10−5 m) and ATP (10−4 m), may be dependent on the synthesis of a prostaglandin‐like substance.