Characterization of receptors involved in the direct and indirect actions of prostaglandins E and I on the guinea‐pig ileum

Abstract

1 A study of the effects of prostaglandin E2 (PGE2) and eleven synthetic analogues on the guinea-pig isolated ileum preparation has revealed three distinct contractile actions, each associated with a different prostaglandin E (EP-) receptor subtype. In addition, PGI2 (prostacyclin) and its stable analogues can activate prostaglandin I (IP-) receptors to elicit both contraction and relaxation of the ileum. The contractile action of 17-phenyl-co-trinor PGE2 on the ileum is unaffected by morphine. Since this analogue shows only weak agonist activity on the rabbit jugular vein (EP2 preparation) and guinea-pig vas deferens (EP3), it may be a more useful standard agonist than PGE2 in EPl1-receptor studies. 5In the presence of morphine and AH 6809, cicaprost inhibits histamine-induced contractions (IC25 = 22 nM). PGI2 and iloprost show mixed inhibitory/potentiating actions, whereas carbacyclin only potentiates histamine contractions. This IP-receptor-mediated inhibition may account for the bell-shaped log concentration-response curve of cicaprost (no inhibitors present) and the very marked block of iloprostinduced contractions by AH 6809. 6 We have found no evidence for either IP-receptors mediating direct contraction or EP-receptors mediating inhibition of the ileum longitudinal smooth muscle, as has been suggested in the literature. 7 In view of the complexity of prostanoid action on the guinea-pig ileum we feel that the preparation must be used with caution to ascertain the EPl agonist or antagonist potencies of novel compounds.

Inhibition of vagally mediated gastric acid secretion by activation of central prostanoid EP3 receptors in urethane‐anaesthetized rats

“…Butaprost behaves as a selective EP2 receptor agonist with relatively low potency (agonist potencies: EP2> > > EP,) (Gardiner, 1986). In the present experiments, misoprostol and sulprostone (0.1, 0.3 (Dong et al, 1986; bition was pre- Lawrence et al, 1989;1992 (Ferreira et al, 1978;Kandasamy & Williams, 1982 In the central nervous suystem, EP3 receptor mRNA is highly expressed in brain regions such as the preoptic area, hypothalamus, locus coeruleus and raphe nuclei (Sugimoto et al, 1994). Administration of PGE2 into specific brain areas of the hypothalamus such as ventromedial hypothalamus and paraventricular nucleus of hypothalamus has been shown to inhibit stimulated gastric acid secretion (Barocelli et al, 1991).The paraventricular nucleus of the hypothalamus is a major site sending signals to the spinal sympathetic preganglionic neurones (Swanson & Sawchenko, 1983).…”

IP Receptor Agonist–Induced DNA Synthesis and Proliferation in Primary Cultures of Adult Rat Hepatocytes: the Involvement of Endogenous Transforming Growth Factor-α

“…Although cAMP generation is generally regarded as the sole signal transduction system of IP receptors, there have been several reports that PGI 2 and its analogs cause increases in intracellular Ca 2+ levels and evoke smooth muscle contraction (28,29). In addition, IP-receptor agonist-induced inositol phosphate breakdown and inositol trisphosphate formation have also been reported in mouse thymus medulla (15).…”

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone

“…Similarly, the relaxations induced by ACh via endogenous release of PGI 2 were also increased in human pulmonary veins treated with the EP 1 antagonists (AH6809, SC19220). Other studies have indicated the ability of PGI 2 to activate EP 1 -receptor in human cells (Walsh & Kinsella, 2000) or to contract guinea-pig smooth muscle via the EP 1 -receptor (Dong et al, 1986;Lawrence et al, 1992). This dual control of the venous tone via EP 1 -and/or IP-receptor in the human lung seems also present in the human hand vein (Arner & Hogesta¨tt, 1991).…”