The action of ketonic prostaglandins on the guinea‐pig myometrium

Clegg, P. Catherine; Hall, William J.; Pickles, V. R.

doi:10.1113/jphysiol.1966.sp007855

Cited by 85 publications

(28 citation statements)

References 18 publications

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“…Small concentrations of prostaglandin E2 potentiated both the contractions evoked directly by stimulation of smooth muscle and indirectly via the parasympathetic nerve supply in control as well as in at-MPT pretreated guinea-pigs. Thus, the ability of prostaglandin E2 to potentiate all types of contractions is in good agreement with the view that the action of prostaglandin involves a direct smooth muscle component (Clegg, Hall & Pickles, 1966;Harry, 1968;Bennett et al, 1968;Eckenfels & Vane, 1972;Eagling, Lovell & Pickles, 1972 (Vane, 1971) the results suggest that the normal concentration of prostaglandin is important for these contractions. A direct inhibition of smooth muscle contraction by indomethacin does not seem to be probable since a small dose of indomethacin was used (Northover, 1971) and moreover the effect of actylcholine was not affected.…”

Section: Discussionsupporting

confidence: 76%

A Modulating Role of Prostaglandins in Contractions of the Guinea‐pig Ileum

Kadlec

Mašek

Šeferna

1974

British J Pharmacology

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1The role of prostaglandins in contractions of the guinea-pig ileum evoked either directly by acetylcholine or indirectly by angiotensin and by coaxial stimulation has been investigated. 2 Prostaglandin E2 in low concentration (6 nM) slightly augmented both types of contraction. Indomethacin, an inhibitor of prostaglandin synthesis, markedly reduced the indirectly evoked contractions but did not affect contractions in response to acetylcholine. The addition of prostaglandin E2 to the preparation treated previously with indomethacin restored the effect of indirect stimulation. 3 The pretreatment of the preparation with guanethidine or a-methyl-p-tyrosine prevented the inhibitory effect of indomethacin on indirectly evoked contractions. Prostaglandin E2 addition to such preparations considerably augmented both types of contraction. 4 The stimulation of non-cholinergic, non-adrenergic inhibitory nerves in the taenia coli and ileum preparations evoked hyperpolarization and relaxation of the preparations followed by action potentials and contraction. These responses were not changed by indomethacin pretreatment and prostaglandin E2, but rebound contraction was sometimes augmented by the prostaglandin. 5 Two mechanisms for the effects of prostaglandin E2 are suggested: a direct effect on smooth muscle, and an indirect action through the sympathetic nerves which by release of noradrenaline affect the acetylcholine release from parasympathetic nerve endings.

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Section: Discussionsupporting

confidence: 76%

A Modulating Role of Prostaglandins in Contractions of the Guinea‐pig Ileum

Kadlec

Mašek

Šeferna

1974

British J Pharmacology

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“…Changing the membrane permeability may be one of the most significant actions of PG. Thus, the direct effect described by Clegg et al (13) may not be due to the result of depolarization but rather to the increase of con ductance of the cell membrane.…”

Section: Discussionmentioning

confidence: 97%

“…There was a latent period (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) sec) in the onset of action of the PG and the PG action lasted longer in comparison with that of ACh. The intracellular mechanism of action of the PG cannot be disregarded.…”

Section: Discussionmentioning

confidence: 99%

“…Bennet et al (12) stated that PGE1 and E2 seemed to stimulate both the intrinsic cholinergic nerves and intestinal smooth muscle cells. Clegg et al (13) elucidated the mechanism of action of Ketogenic PGs (Ei and E2) on the myometriurn, by means of Kymographic, electrical field stimulation and single sucrose-gap methods, and con cluded that PGE1 and E2 have two different kinds of effects; the direct and enhancement.…”

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confidence: 99%

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The Mechanism of Action of Prostaglandin F2α on the Smooth Muscle of Guinea-Pig Taenia Coli

Ouji

1974

Japanese Journal of Pharmacology

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Abstract-The effect of prostaglandin F_2α(PGF_2α on isolated smooth muscle of guinea-pig taenia coil as related to cholinergic and adrenergic receptors of the muscle was investigated using the double sucrose-gap method. PGF_2α in the concentration of 1.0×10^-6 g/ml caused and augmented the contraction of the smooth muscle by depo larizing the membrane, decreasing the membrane resistance, and increasing the fre quency of spike generation. These actions were not abolished by atropine sulfate (10^-7 g/ml), phentolamine (10^-6 g/ml), propranolol (10^-6 g/ml), respectively. PGF_2α had the same action as that of acetylcholine on the contraction of the smooth mus cle, but the onset was slower and the duration longer. The inhibitory effects of ad renaline (10^-7 g/ml), noradrenaline (10^-7 g/ml), and isoproterenol (10^-7 g/ml) were not suppressed by treatment with PGF_2α. These results indicate that the effect of PG was not mediated either by the cholinergic nor the adrenergic receptors (α and β receptors), and it is suggested that PGF_α2 may act on sites of the cell membrane other than adrenergic and cholinergic receptors to increase the membrane conduct ance as well as in the intracellular mechanism for the induction and augmentation of contraction of the tacnia coli smooth muscle. The interrelationship of the PG and Ca ion is also discussed.It is well known that prostaglandins (PGs) are widely distributed in animal tissues The former is postulated to result from depolarization at the exposed cell membrane whereas the latter may result from facilitation of excitation contraction coupling. The present experiment was carried out by the application of a double sucrose-gap method to

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“…In a few instances, it was as marked and as prolonged as the 'enhancement' following the application of prostaglandin El or E2 to the guinea-pig myometrium (Clegg, Hall & Pickles, 1966); whereas in other experiments it was absent or led rapidly into a period of decreased responses. This variability was not studied in detail.…”

Section: Potentiation Ofother Spasmogensmentioning

confidence: 95%

Spasmogenic and Potentiating Actions of Some Amino Acids on the Guinea‐pig Myometrium

Bedwani

Ishizawa

Pickles

et al. 1977

British J Pharmacology

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I Thirty-three amino acids were applied separately in concentrations of 2 to 10 mM to guinea-pig uterine horns in vitro at pH 7.4. About half the acids regularly produced contractions. 2 Glycine and the straight-chain L-a-amino acids up to norleucine were active (longer ones not tested); D-isomers were less potent or inactive in these concentrations. The co-amino acids yaminobutyric acid (GABA) and 6-aminovaleric, and the a,o-diamino acids L-a, P-diaminopropionic and L-a,y-diaminobutyric were active, whereas others of similar chain-length such as f,-alanine and lysine were not. The diacidic acids, glutamic and homocysteic, were more active than the amido-amino acids, glutamine and asparagine. Histidine and phenylalanine showed little or no activity. 3 The use of appropriate blocking agents indicated that the responses to representative acids were not mediated by histamine, 5-hydroxytryptamine, acetylcholine, noradrenaline or by prostaglandins. Attempts to block the actions of glycine and GABA with strychnine, thebaine, picrotoxin, bicuculline or tetramethylenedisulphotetramine (TETS) were unsuccessful. 4 When some of the acids that were spasmogenic at 2 to 10 mm were applied at sub-spasmogenic doses, they transiently potentiated other spasmogens such as oxytocin or acetylcholine. This effect was also shown by a mixture of amino acids at approximately the normal plasma concentrations. 5 There is some similarity between the spasmogenic activities of different amino acids and their known abilities to depolarize neurones.

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The action of ketonic prostaglandins on the guinea‐pig myometrium

Cited by 85 publications

References 18 publications

A Modulating Role of Prostaglandins in Contractions of the Guinea‐pig Ileum

A Modulating Role of Prostaglandins in Contractions of the Guinea‐pig Ileum

The Mechanism of Action of Prostaglandin F2α on the Smooth Muscle of Guinea-Pig Taenia Coli

Spasmogenic and Potentiating Actions of Some Amino Acids on the Guinea‐pig Myometrium

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