Effects of indomethacin, piroxicam and selected prostanoids on gastric acid secretion by the rat isolated gastric mucosa

Reeves, J.J.; Stables, R.

doi:10.1111/j.1476-5381.1985.tb08945.x

Cited by 44 publications

(25 citation statements)

References 21 publications

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“…The rank order of affinity of prostanoid agonist binding to porcine mucosal cell membranes has been shown (Beinborn et al, 1988) to be similar to the rank order of agonist potency defined in functional assays by Coleman et al (1985) for the presence of an EP receptor. Similar findings have been obtained in functional studies by Reeves & Stables (1985) who used isolated parietal cells and gastric muscosal sheets, respectively. However, further characterization of the EP receptor subtype present on the parietal cells is complicated by the existence of three putative subtypes of this receptor, denoted as EP1, EP2 and EP3 Some workers have proposed that TP receptors may also play a role in the inhibition of gastric acid secretion (see Reeves & Stables, 1985 for references), although part of the effect of TP agonists appears to be indirect (Reeves & Stables, 1987).…”

Section: Discussionsupporting

confidence: 76%

“…Similar findings have been obtained in functional studies by Reeves & Stables (1985) who used isolated parietal cells and gastric muscosal sheets, respectively. However, further characterization of the EP receptor subtype present on the parietal cells is complicated by the existence of three putative subtypes of this receptor, denoted as EP1, EP2 and EP3 Some workers have proposed that TP receptors may also play a role in the inhibition of gastric acid secretion (see Reeves & Stables, 1985 for references), although part of the effect of TP agonists appears to be indirect (Reeves & Stables, 1987). However, the evidence is controversial since other studies have shown that TP agonists are either ineffective (Tao & Wilson, 1984) or, when given by close injection into the gastric artery, can cause gastric mucosal damage (Espulugues & Whittle, 1988).…”

Section: Discussionsupporting

confidence: 76%

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Characterization of the prostanoid receptor profile of enprostil and isomers in smooth muscle and platelets in vitro

Eglen¹,

Whiting²

1989

British J Pharmacology

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1 Enprostil is composed, in approximately equal proportions, of 4 allenic isomers which are prostanoids structurally related to prostaglandin E2 (PGE2). The isomers are denoted as RS-86505-007, RS-86812-007 which are in the 'natural' R and S configuration (with respect to PGE2) and RS-86505-008 and RS-86812-008 which are in the 'unnatural' R and S configuration. In the present study we have characterized their activity at prostanoid receptors, in vitro.2 Enprostil acted as a highly potent (-log EC50 = 8.30 + 0.08; mean + s.e.mean, n = 6) EP3 receptor agonist in the guinea-pig vas deferens, although no activity was observed at guinea-pig tracheal EP2 receptors at concentrations up to and including 1OgM. Attempts to study the action of enprostil at EP1 receptors were complicated by a general increase in the spontaneous activity of the guinea-pig isolated ileum. This response was stereospecific (i.e. observed, with the 'natural' R and S isomers only) and was not mediated through EP1, FP or TP receptors. 3 Enprostil also exhibited a potent agonist effect at FP and TP receptors in the rat colon and guinea-pig aorta (-log EC50 values = 7.34 + 0.11 and 6.54 + 0.07, mean + s.e.mean, n = 4-8 respectively). No activity at concentrations up to and including 10pM was observed at DP or IP receptors in the guinea-pig platelet mediating inhibition of ADP-induced aggregation. 4 A similar profile was observed with the 'natural' R and S allenic isomers of enprostil (RS-86505-007 and RS-86812-007, respectively); RS-86505-007 was between 4 and 10 fold more potent than the racemic enprostil. The 'unnatural' allenic R and S isomers of enprostil were much less potent than enprostil, with the latter being virtually inactive. 5 Enprostil and the 'natural' R and S isomers, therefore, were EP3, FP and TP agonists, being most potent at the EP3 receptor. The preferred configurations for these receptors appears to be the R, and to a lesser extent the S, form of the natural allenic isomer. The effect of enprostil at EP1 receptors was not characterized in view of the presence of excitatory EP3 receptors in the guineapig ileum. These data were in accordance with the pharmacological activity of enprostil, including inhibition of gastric acid secretion (possibly EP3) and diaorrhea (possibly TP).

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 76%

Characterization of the prostanoid receptor profile of enprostil and isomers in smooth muscle and platelets in vitro

Eglen¹,

Whiting²

1989

British J Pharmacology

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“…The ionic compositions (mM) of the solutions were:-serosal: NaCI 118.5, NaHCO3 25.0, KCl 4.7, MgSO4 0.6, KH2PO4 1.2, CaCl2 1.3 and glucose 11.1. Indomethacin has been shown previously to enhance the responsiveness to secretagogues of the RGM (Reeves & Stables, 1985) The non-peptidic antagonists lorglumide, devazepide and Following a priming concentration of pentagastrin (100 nM), subsequent concentration-response curves were reproducible with first and second curves producing EC50 values of 27 (15-49) and 21 (9-46) nm and maxima of 133 ± 34 and 136 ± 29 nmol H+ min-' (n = 4) respectively. The effects of gastrin/CCK peptides on acid secretion were determined in the presence of the peptidase inhibitors phosphoramidon…”

Section: Methodsmentioning

confidence: 74%

“…Rat isolated gastric mucosa Acid secretion was measured from rat isolated gastric mucosa (RGM) prepared as described by Reeves & Stables (1985). Sprague-Dawley rats weighing 90-1I0 g were anaesthetized with sodium pentobarbitone (60 mg kg-', i.p.).…”

Section: Methodsmentioning

confidence: 99%

Functional comparisons of gastrin/cholecystokinin receptors in isolated preparations of gastric mucosa and ileum

Patel¹,

Spraggs²

1992

British J Pharmacology

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The gastrin cholecystokinin (CCK) receptors mediating stimulation of acid secretion in rat isolated gastric mucosa (RGM) and contraction in guinea‐pig isolated ileum longitudinal muscle‐myenteric plexus (GPI) have been characterized by use of peptide agonists and the non‐peptide antagonists, lorglumide, devazepide and L‐365,260. In RGM, gastrin peptides (sulphated gastrin heptadecapeptide (G‐17), non‐sulphated (ns) G‐17 and pentagastrin) were potent agonists of acid secretion (EC50 values of 4.3, 16 and 27 nm respectively). Sulphated CCK octapeptide (CCK‐8) was also a potent agonist, (EC50 = 0.9 nm), but was less efficacious, producing a lower maximal response. In contrast, in GPI, CCK‐8 was a potent full agonist (EC50= 1.4 nm) and was more than 1000 times more potent than the gastrin peptides in producing a sustained contractile response. In GPI, CCK‐8 (0.1 to 100 nm) produced sustained contractile responses, whilst CCK‐4 (3 to 1000 nm) produced transient responses. These responses had different sensitivities to atropine (1 μm), suggesting that more than one receptor may mediate contraction in this tissue. In RGM, L‐365,260 was the most potent antagonist of pentagastrin‐stimulated acid secretion (pA2 = 7.6). This functional affinity estimate was similar to that for L‐365,260 as an antagonist of excitatory responses in rat ventromedial hypothalamic slices (Kemp et al., 1989) but differed from binding affinity estimates in guinea‐pig cortex and gastric glands (Freidinger, 1989). In GPI, devazepide, L‐365,260 and lorglumide yielded different affinity estimates when compared against CCK‐8 and CCK‐4 or pentagastrin respectively. These studies were consistent with the view that the sustained response produced by CCK‐8 was mediated by CCKA receptors and the transient response produced by CCK‐4 and pentagastrin was mediated by CCKB receptors. Affinity estimates for L‐365,260 and lorglumide against CCK‐4 or pentagastrin in GPI were significantly different from corresponding estimates against pentagastrin in RGM. These studies are consistent with the view that gastrin/CCKB receptors in GPI may differ from those in RGM.

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“…PGE2 has been shown to stimulate the rate of bone resorption induced by the parathyroid hormone (MacDonald, 1986). In rat gastric mucosa, PGE2 causes inhibition of gastric acid secretion in the parietal cell but stimulates gastric nonparietal secretion (Reeves and Stables, 1985;Major and Scholes, 1978;Soll, 1980;Wollin et al, 1979). In the amphibian cornea, both E and F prostaglandins stimulate er transport across the epithelium, and thus contribute to the maintenance of corneal transparency (Beitch et al, 1974;Bentley and McGahen, 1982).…”

Section: Biological Actions Of Pge2mentioning

confidence: 99%

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

Qian¹

1997

Insect Biochemistry and Molecular Biology

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Effects of indomethacin, piroxicam and selected prostanoids on gastric acid secretion by the rat isolated gastric mucosa

Cited by 44 publications

References 21 publications

Characterization of the prostanoid receptor profile of enprostil and isomers in smooth muscle and platelets in vitro

Characterization of the prostanoid receptor profile of enprostil and isomers in smooth muscle and platelets in vitro

Functional comparisons of gastrin/cholecystokinin receptors in isolated preparations of gastric mucosa and ileum

A specific prostaglandin E2 receptor and its role in modulating salivary secretion in the female tick, Amblyomma americanum (L.)

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