Prostacyclin analogues inhibit canine parietal cell activity and cyclic AMP formation

To assess further the mechanism by which prostacyclin inhibits acid secretion, the actions of two stable prostacyclin analogues on parietal cell function and cyclic AMP formation were tested using enzymatically dispersed cells from canine fundic mucosa. Accumulation of ¹⁴C-aminopyrine (AP) was used as an index of parietal cell response to stimulation. The 16-phenoxy derivative of PGI₂ inhibited accumulation of AP stimulated by histamine (10 μM), with 50% inhibition (ID₅₀) at 10 nM. 6_β-PGI₁ also inhibited the action of histamine (ID₅₀ 0.5μM) but failed to block stimulation by carbachol or the dibutyryl derivative of cyclic AMP (dbcAMP). In similiar concentrations to those producing inhibition of histamine-stimulated AP accumulation, the 16-phenoxy analogue and 6_β-PGI₁ inhibited histamine-stimulated cyclic AMP generation by parietal cells. At 100 fold higher concentrations, 6_β-PGI₁ stimulated cyclic AMP formation, presumably in non-parietal cells. Even in high concentrations the 16-phenoxy analogue failed to increase cyclic AMP formation by mucosal cells. These data indicate that the stable prostacyclin analogues are potent, direct inhibitors of histamine-stimulated parietal cell function and that it is the inhibition, rather than the stimulation, of cyclic AMP formation that is linked to the antisecretory actions of these prostanoid compounds.     

Investigation of the vascular actions of arachidonate lipoxygenase and cyclo-oxygenase products on the isolated perfused stomach of rat and rabbit

The vascular actions of several prostanoids and arachidonate lipoxygenase products were investigated on the gastric circulation of rat and rabbit perfused with Kreb's solution. Under resting conditions, prostacyclin and PGE₂ produced small decreases in perfusion pressure with prostacyclin being the more potent. During vasoconstriction induced by infusion of noradrenaline, vasopressin or angiotensin II, prostacyclin was 20–40 times as active as PGE₂ as a gastric vasodilator in rat or rabbit stomach. PGF_2α was a less potent vasoconstrictor than noradrenaline, while the epoxy-methano endoperoxide analogue produced a long-lasting vasoconstriction. The putative metabolite, 6-oxo-PGE₁ was less active than prostacyclin as a vasodilator, having comparable activity to PGE₁, whereas 6-oxo-PGF_1α had very little activity. The endoperoxide, PGH₂ reduced perfusion pressure, this effect being inhibited by concurrent infusion of 15-HPETE. The vasodilation induced by arachidonic acid was likewise reduced by 15-HPETE, and abolished by indomethacin infusion. The arachidonate lipoxygenase hydroperoxides were vasodilator in the gastric circulation, the rank order of potency being 12-HPETE > 11-HPETE > 5-HPETE > 15-HPETE in both rat and rabbit stomach. It is possible that such vasoactive lipoxygenase products, may play modulator roles in the gastric mucosa.     

Metal-metal bonding and charge localisation in [Ru2X9], X=Cl or Br; n=1, 2, 3, 4. A spectroelectrochemical study

A spectroelectrochemical study of [Ru₂X₉]ⁿ⁻, X=Cl, Br; n=1, 2, 3, 4 has been undertaken. Stable solutions of n=4, 2, 1 can be formed by electrolysis at low temperatures. Analysis of the Vis-NIR spectra of the complexes indicate that the Ru^II---R^III dimers (n=4) have delocalised mixed valence and that the Ru^III---R^III (n=3) dimers have a strong Ru---Ru bond. The more oxidised materials do not form a Ru---Ru bond; the spectroscopic data indicates the Ru^III---R^IV dimers have localised valency.