Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents

Tolman, E.L.; Partridge, Ruth

doi:10.1016/0090-6980(75)90139-2

Cited by 77 publications

(21 citation statements)

References 11 publications

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“…also preferentially antagonize contractions of gerbil, guinea-pig or human gastro-intestinal muscle to certain prostaglandins (Tolman & Partridge, 1975;Famaey et al, 1977;Bennett, Pratt & Sanger, 1980). In human myometrium the drugs did not consistently antagonize submaximal contractions to ACh or PGF22 but greatly reduced those to the PGH2 analogue, U-46619 .…”

Section: Discussionmentioning

confidence: 98%

Antagonism of Prostanoid‐induced Contractions of Rat Gastric Fundus Muscle by Sc‐19220, Sodium Meclofenamate, Indomethacin or Trimethoquinol

Bennett

Jarosik

Sanger

et al. 1980

British J Pharmacology

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3 The effect of the cyclo-oxygenase inhibitor sodium meclofenamate, 1 or 2 1tg/ml, on 6,15-diketo-PGFl, or thromboxane B2 was similar to the small antagonism of ACh, whereas the other prostanoids were blocked to greater extents. Indomethacin, 1 jig/ml, also reduced contractions to the prostanoids, but antagonism of the PGH2 epoxymethano analogues was considerably less than with meclofenamate. 4 The ,B-adrenoceptor stimulant trimethoquinol, 50 ng/ml, was the most potent prostanoid antagonist tested; all the prostanoids except PGE2 were antagonized more than ACh.

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Section: Discussionmentioning

confidence: 98%

Antagonism of Prostanoid‐induced Contractions of Rat Gastric Fundus Muscle by Sc‐19220, Sodium Meclofenamate, Indomethacin or Trimethoquinol

Bennett

Jarosik

Sanger

et al. 1980

British J Pharmacology

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“…Furthenoore, the central hypotensive effect of PGI 2 was antagonised by sodium meclofenamate (13). Indomethacin has been repqrted to blunt the PGDz-induced contractions of the longitudinal nruscle of rat gastric fundus (12) and to reduce submaximal contractions to PGE 1 in gerbil colon (23). Antagonism of the prostaglandin action by indumethacin has also been demonstrated in rat uterus (24) and in isolated guinea-pig ileum and rabbit ear preparations (25).…”

Section: Effects Of Indomethacin and Sodium Meclofenamatementioning

confidence: 97%

Central cardiovascular and thermal effects of prostaglandin D2 in rats

Sirén

1982

Prostaglandins, Leukotrienes and Medicine

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Prostaglandin Dz (PGD z ) is the most common prostaglandin type of tile rat brain. Recently a neurornodulator role for PGD z has been suggested. In the present work the central cardiovascular and thermal effects of PGDz were studied in urethane-anaesthetised rats. Mlen adrndnistered at the doses of 0.001-10 ~g/rat into the lateral cerebral ventricle(i.c.v.), PGD2 slightly increased the blood pressure, heart rate and body ternperaure.The highest dose caused also an initial hypotensive effect. Upon lntravenous injections PGD2 (0.1-10 ~g/rat) initially decreased and then weakly increased the blood pressure but had only negligible effects on heart rate and body temperature. Central pretreatment with sodium meclofenamate or indomethacin (1 mg/rat i.c.v.) antagonised effectively all the recorded central effects of PGD2.The central cardiovascular and thermal effects of PGD 2 were much weaker than those obtained earlier with other prostaglandins, such as PGF2a. and PGE2.. Therefore, in spite of its ablUldance in the brain PGD 2 may not be very important for the central cardiovascular and thermal regulation in the rat.

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“…However, the antagonism of Ca2+ contrac ture by Indo in our depolarized strips was of a noncompetitive nature, which suggests that Indo may be acting by a different mechanism since Feinstein (5) has shown that local anes thetics act in a competitive nature to antago nize calcium contracture in potassium de polarized rat uterine horns. Tolman and Par tridge (15) have shown that certain anti inflammatory agents, such as fenbufen, have antispasmodic activity similar to other anti inflammatory agents yet lack activity as prosta glandin syn diesis inhibitors. They have sug gested that Indo and other anti-inflammatory agents may act at several sites and one of these may be a common receptor for prostaglandin.…”

Section: Discussionmentioning

confidence: 99%

Interactions of Calcium, Prostaglandins and Indomethacin on the Smooth Muscle of the Bladder

Anderson¹,

Kohn²

1978

Pharmacology

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The effects of prostaglandin (PG) E₂, PGF_2α and indomethacin (Indo) were studied on isolated detrusor smooth muscle strips in balanced salt solution and in 80 mΛf K⁺ depolarizing solution. The addition of Indo to the smooth muscle preparation at concentrations of 0.1 to 1.0 μM produced depression of spontaneous motility that was partially antagonized by PGE₂ or by elevating the extracellular Ca²⁺ level. Alone, both PGE₂ and Ca²⁺ caused a marked increase in motility, increasing both frequency and amplitude. In low Ca²⁺, K⁺ depolarized bathing medium with 0.1 m/kf EGTA added PGE₂ or PGF_2α augmented Ca²⁺ contractures both in velocity and amplitude while either PG without Ca²⁺ had no effect on the smooth muscle. Indo produced a noncompetitive antagonism of the Ca²⁺ dose response curve in 80 mM/ K⁺ depolarized preparations suggesting a direct effect on Ca²⁺ flux. Also Indo depressed both PG and Ca²⁺ contractures in terms of velocity and magnitude, suggesting that Indo may act at Ca²⁺ channels in addition to its action on PG synthetase. These data support the work of others who suggest that PGs may augment Ca²⁺ permeability, acting at the Ca²⁺ channel or as a carrier for Ca²⁺ across smoth muscle cell membranes.

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Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents

Cited by 77 publications

References 11 publications

Antagonism of Prostanoid‐induced Contractions of Rat Gastric Fundus Muscle by Sc‐19220, Sodium Meclofenamate, Indomethacin or Trimethoquinol

Antagonism of Prostanoid‐induced Contractions of Rat Gastric Fundus Muscle by Sc‐19220, Sodium Meclofenamate, Indomethacin or Trimethoquinol

Central cardiovascular and thermal effects of prostaglandin D2 in rats

Interactions of Calcium, Prostaglandins and Indomethacin on the Smooth Muscle of the Bladder

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