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

Bennett, A. B.; Jarosik, C.; Sanger, Gareth J.; Wilson, David

doi:10.1111/j.1476-5381.1980.tb10922.x

Cited by 23 publications

(15 citation statements)

References 21 publications

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“…adminIstered PGDz• In agreement with the present findings an antagonism of the effects of exogenous prostaglandins by fenarnates and indomethacin has been reported in several tissues: Sodium meclofenamate and other fe~amate7 antagonise th: effects of exogenous prostaglandins in rat, gumea-plg and human allJl'entary muscle (11,12), human bronchial nruscle (20)! an~ these drugs attenuate the PGF 2 a-induced bradycardia and hypoenslon ln the cat· (21) and prostaglandin-induced gastric acid secretion ill the rat (22).…”

Section: Effects Of Indomethacin and Sodium Meclofenamatesupporting

confidence: 90%

“…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%

“…to the urethane-anaesthetIsed rat In order to obtain complete simultaneous cumulative dose-response curves for blood pressure, heart rate and body temperature. Since sodi~ mec1o-fenamate interferes with the effects of exogenous prostaglandlns both in the peripheral tissues (11,12) and in the brain (4,13), it seemed worthwhile to investigate the influence of this agent on the central effects of PGD z . For comparison, the effect of indomethacin, an equally effective inhibitor of prostaglandin synthesis as sodium meclofenamate (14), was also studied.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Effects Of Indomethacin and Sodium Meclofenamatesupporting

confidence: 90%

Section: Effects Of Indomethacin and Sodium Meclofenamatementioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Central cardiovascular and thermal effects of prostaglandin D2 in rats

Sirén

1982

Prostaglandins, Leukotrienes and Medicine

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“…Indeed, the EP 1 receptor antagonist SC19220 caused a statistically significant inhibition of contraction to both iloprost and beraprost. These data are consistent with the findings of Bennett et al (1980). DBTSA may also antagonize TP and DP receptors at the concentration used in this study (Gallant et al, 2002).…”

Section: Selexipag and Gastric Function 253supporting

confidence: 82%

“…gastric fundus as evidenced by contraction to the EP 3 /EP 1 receptor agonist sulprostone (Bennett et al, 1980). Furthermore, contraction of rat fundal strips (Dong et al, 1986) and guinea pig ileum (Lawrence et al, 1992) to PGI 2 analogs has been reported.…”

Section: Introductionmentioning

confidence: 99%

Selexipag: A Selective Prostacyclin Receptor Agonist that Does Not Affect Rat Gastric Function

Morrison¹,

Ernst²,

Hess³

et al. 2010

J Pharmacol Exp Ther

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Selexipag [2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N-(methylsulfonyl)acetamide] is an orally available prostacyclin (PGI 2 ) receptor (IP receptor) agonist that is chemically distinct from PGI 2 and is in clinical development for the treatment of pulmonary arterial hypertension. Selexipag is highly selective for the human IP receptor in vitro, whereas analogs of PGI 2 can activate prostanoid receptors other than the IP receptor. The goal of this study was to determine the impact of selectivity for the IP receptor on gastric function by measuring 1) contraction of rat gastric fundus ex vivo and 2) the rates of gastric emptying and intestinal transport in response to selexipag in comparison with other PGI 2 analogs. The rat gastric fundus expresses mRNA encoding multiple prostanoid receptors to different levels: prostaglandin E receptor 1 (EP 1 ) Ͼ prostaglandin E receptor 3 (EP 3 ), IP receptor Ͼ prostaglandin D 2 receptor 1, thromboxane receptor. Selexipag and metabolite {4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (ACT-333679) did not contract gastric fundus at concentrations up to 10 Ϫ3 M. In contrast, the PGI 2 analogs iloprost and beraprost evoked concentration-dependent contraction of gastric fundus. Contraction to treprostinil was observed at high concentration (10 Ϫ4 M). Contraction to all PGI 2 analogs was mediated via activation of EP 3 receptors, although EP 1 receptors also contributed to the contraction of gastric fundus to iloprost and beraprost. Antagonism of IP receptors did not affect responses. Oral selexipag did not significantly alter gastric function in vivo, as measured by rates of stomach emptying and intestinal transport, whereas beraprost slowed gastrointestinal transport. The high functional selectivity of selexipag and ACT-333679 for the IP receptor precludes a stimulatory action on gastric smooth muscle and may help minimize gastric side effects such as nausea and vomiting.

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Docosahexaenoic acid and eicosapentaenoic acid strongly inhibit prostanoid TP receptor‐dependent contractions of guinea pig gastric fundus smooth muscle

Shimizu

Murai

et al. 2022

Pharmacology Res & Perspec

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The inhibitory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and linoleic acid (LA) on the contractions induced by five prostanoids and U46619 (a TP receptor agonist) were examined in guinea pig gastric fundus smooth muscle (GFSM). Tension changes were isometrically measured, and the mRNA expression of prostanoid receptors was measured by RT‐qPCR. DHA and EPA significantly inhibited contractions induced by the prostanoids and U46619, whereas LA inhibited those induced by prostaglandin D 2 and U46619. The mRNA expression levels of the prostanoid receptors were TP ≈ EP 3 >> FP > EP 1 . The inhibition by DHA, EPA, and LA was positively correlated with that by SQ 29,548 (a TP receptor antagonist) but not with that by L‐798,106 (an EP 3 receptor antagonist). DHA and EPA suppressed high KCl‐induced contractions by 35% and 25%, respectively, and the contractions induced by the prostanoids and U46619 were suppressed by verapamil, a voltage‐dependent Ca 2+ channel (VDCC) inhibitor, by 40%–85%. Although LA did not suppress high KCl‐induced contractions, it suppressed U46619‐induced contractions in the presence of verapamil. However, LA did not show significant inhibitory effects on U46619‐induced Ca 2+ increases in TP receptor‐expressing cells. In contrast, LA inhibited U46619‐induced contractions in the presence of verapamil, which was also suppressed by SKF‐96365 (a store‐operated Ca 2+ channel [SOCC] inhibitor). These findings suggest that the TP receptor and VDCC are targets of DHA and EPA to inhibit prostanoid‐induced contractions of guinea pig GFSM, and SOCCs play a significant role in LA‐induced inhibition of U46619‐induced contractions.

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

Cited by 23 publications

References 21 publications

Central cardiovascular and thermal effects of prostaglandin D2 in rats

Central cardiovascular and thermal effects of prostaglandin D2 in rats

Selexipag: A Selective Prostacyclin Receptor Agonist that Does Not Affect Rat Gastric Function

Docosahexaenoic acid and eicosapentaenoic acid strongly inhibit prostanoid TP receptor‐dependent contractions of guinea pig gastric fundus smooth muscle

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