ANTAGONISM OF PROSTANOID‐INDUCED CONTRACTIONS OF RAT GASTRIC FUNDUS MUSCLE BY SC‐19220, SODIUM MECLOFENAMATE, INDOMETHACIN OR TRIMETHOQUINOL

1 The effects of SC‐19220, sodium meclofenamate, indomethacin or trimethoquinol were studied on contractions of the rat stomach longitudinal muscle to prostaglandin D2 (PGD2), PGE2, PGF2α, PGH2, epoxymethano PGH2 analogues, PGI2, 6‐keto‐PGF1α, 6,15‐diketo‐PGF1α and thromboxane B2. All the drugs reduced contractions to all the prostanoids, but the degree of reduction differed widely. Selectivity of blockade was assessed by comparison with acetylcholine (ACh). 2 With SC‐19220 5 μg/ml the effect on thromboxane B2, PGD2 or PGH2 and its epoxymethano analogues was not significantly different from the small effect on ACh, but the other prostanoids were blocked to greater extents. 3 The effect of the cyclo‐oxygenase inhibitor sodium meclofenamate, 1 or 2 μg/ml, on 6,15‐diketo‐PGF1α or thromboxane B2 was similar to the small antagonism of ACh, whereas the other prostanoids were blocked to greater extents. Indomethacin, 1 μg/ml, also reduced contractions to the prostanoids, but antagonism of the PGH2 epoxymethano analogues was considerably less than with meclofenamate. 4 The β‐adrenoceptor stimulant trimethoquinol, 50 ng/ml, was the most potent prostanoid antagonist tested; all the prostanoids except PGE2 were antagonized more than ACh.

[1]  F. Coceani,et al.  On the action of prostaglandin E1 and prostaglandins from brain on the isolated rat stomach. , 1966, Canadian journal of physiology and pharmacology.

[2]  G. Sanger,et al.  Trimethoquinol selectively antagonises longitudinal muscle contractions of rat isolated gastric fundus to thromboxane B2 and epoxymethano analogues of PGH2 [proceedings]. , 1979, British Journal of Pharmacology.

[3]  G. Sanger,et al.  Regional differences in the responses to prostanoids of circular muscle from guinea‐pig isolated intestine , 1980, The Journal of pharmacy and pharmacology.

[4]  G. Sanger,et al.  The effects of prostaglandin D2 on the circular muscle of guinea-pig isolated ileum and colon [proceedings]. , 1978, British journal of pharmacology.

[5]  C. Malmsten Some biological effects of prostaglandin endoperoxide analogs. , 1976, Life sciences.

[6]  E. Horton,et al.  Prostaglandins A1, A2 and 19‐hydroxy A1; their actions on smooth muscle and their inactivation on passage through the pulmonary and hepatic portal vascular beds , 1969, British journal of pharmacology.

[7]  J. Vane,et al.  The effects of prostacyclin (PGI2) on tissues which detect prostaglandins (PG'S). , 1977, Prostaglandins.

[8]  R. Flower Drugs which inhibit prostaglandin biosynthesis. , 1974, Pharmacological reviews.

[9]  L. Sorrentino,et al.  Indomethacin and prostaglandins. , 1972, European journal of pharmacology.

[10]  J. Oates,et al.  The effects of arachidonic acid, prostaglandin E2 and prostaglandin F2alpha on the longitudinal stomach strip of the rat. , 1973, The Journal of pharmacology and experimental therapeutics.

[11]  J. Posner,et al.  Studies on prostaglandin antagonists , 1971, British journal of pharmacology.

[12]  J. Famaey,et al.  Effect of high concentrations of non-steroidal and steroidal antiinflammatory drugs on prostaglandin-induced contractions of the guinea-pig isolated ileum. , 1977, Prostaglandins.

[13]  S. Moncada,et al.  Use of the rabbit transverse stomach-strip to identify and assay prostacyclin, PGA2, PGD2 and other prostaglandins. , 1979, European journal of pharmacology.

[14]  Sanner Jh Antagonism of prostaglandin E2 by 1-acetyl-2-(8-chloro-10,11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl) hydrazine (SC-19220). , 1969 .

[15]  B. Northover,et al.  Effect of anti‐inflammatory drugs on the binding of calcium to cellular membranes in various human and guinea‐pig tissues , 1973, British journal of pharmacology.

[16]  G. Sanger,et al.  Fenamates may antagonize the actions of prostaglandin endoperoxides in human myometrium. , 1979, British journal of clinical pharmacology.

[17]  M. Hamberg,et al.  Prostaglandin endoperoxides IV. Effects on smooth muscle. , 1975, Life sciences.

[18]  J. H. Sanner Antagonism of prostaglandin E2 by 1-acetyl-2-(8-chloro-10,11-dihydrodibenz (b,f) (1,4) oxazepine-10-carbonyl) hydrazine (SC-19220). , 1969, Archives internationales de pharmacodynamie et de therapie.

[19]  H. Collier,et al.  Antagonism by Fenamates of Prostaglandin F2α and of Slow Reacting Substance on Human Bronchial Muscle , 1968, Nature.

[20]  H. Collier,et al.  Specific receptors for prostaglandins in airways. , 1980, Prostaglandins.

[21]  G. Sanger,et al.  ANTAGONISM BY FENAMATES OF PROSTAGLANDIN ACTION IN GUINEA‐PIG AND HUMAN ALIMENTARY MUSCLE , 1980, British journal of pharmacology.

[22]  S. Kishimoto,et al.  Clinical effectiveness of a new bronchodilator, inolin, on bronchial asthma. , 1968, Annals of allergy.

[23]  E. Tolman,et al.  Multiple sites of interaction between prostaglandins and non-steroidal anti-inflammatory agents. , 1975, Prostaglandins.

[24]  G. Sanger,et al.  Sodium flufenamate antagonises the potentiation by prostaglandins of noradrenaline-induced vasoconstriction in rat mesentery [proceedings]. , 1979, British journal of pharmacology.