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Leukotrienes C4 and D4 potentiate acid production by isolated rat parietal cells

1989; Elsevier BV; Volume: 97; Issue: 6 Linguagem: Inglês

10.1016/0016-5085(89)90385-5

1528-0012

Wolfgang Schepp, Doris Kath, C. Tatge, B. Zimmerhackl, V. Schusdziarra, Meinhard Classen,

Biochemical Analysis and Sensing Techniques

The effects of leukotrienes (LTs) B,, C,, and D, on acid production by enriched (W&85%) rat parietal cells were investigated.Acid production was indirectly measured by [14C]aminopyrine uptake into the cells.Leukotriene B, (1O-1o-1O-s mol/L) had no effect on basal or prestimulated ['4C]aminopyrine uptake.Leukotriene C, and LTD, (10-'"-10-6 mol/ L) also did not change basal acid production but potentiated prestimulated [14C]aminopyrine up take.Maximal effects were observed with 1 x lo-' mol/L LTC, or with 3 x lo-' moYL LTD,.At these concentrations LTC, and LTD, induced the indicated increases above the responses to the following prestimulants (= 100%): low4 mol/L histamine (71% and 74%, respectively), 10S5 moYL forskolin (54% and 106%), 10m4 mol/L dibutyryl cyclic adenosine monophosphate (34% and al%), and 10m4 mol/L carhamylcholine (160% and 116%).Yet, adenosine triphosphate (2.5-5 x 10V3 mol/L)-induced [14C]aminopyrine uptake in digitonin-permeabilized pari-eta1 cells was not further increased by LTC, or LTD,.At 10d5 mol/L the selective LTD, antagonist L-660,711 (MK-571) reduced the effect of 3 x lo-' mol/L LTD, by 74% but had no effect on the potentiation by LTC,.We conclude that the sulfidopeptide LTs C, and D,, but not LTB,, exert a direct effect on rat parietal cells, and that this effect seems to be mediated by separate specific receptors.Leukotriene C, and LTD, potentiate prestimulated H+ formation by interacting with an intracellular mechanism that is commonly activated upon occupation of histamine H,-as well as muscarinic receptors, and that is also activated by the postrecep tor stimuli forskolin and dibutyryl cyclic adenosine monophosphate; yet, this mechanism seems to be localized proximal to the H+, K+-adenosine triphosphatase.gesting the presence of y-glutamyl transpeptidase in these tissues.As yet the cellular source of gastric LT formation has not been identified.In anesthetized cats exogenous LTC,, LTD,, and LTE, were found to reduce the transgastric potential difference and to stimulate pepsin release while leaving basal acid secretion unchanged: LTB, was ineffective (19,20).By contrast, in innervated, as