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

The effects of leukotrienes (LTs) B4, C4, and D4 on acid production by enriched (80%-85%) rat parietal cells were investigated. Acid production was indirectly measured by [14C]aminopyrine uptake into the cells. Leukotriene B4 (10(-10)-10(-6) mol/L) had no effect on basal or prestimulated [14C]aminopyrine uptake. Leukotriene C4 and LTD4 (10(-10)-10(-6) mol/L) also did not change basal acid production but potentiated prestimulated [14C]aminopyrine uptake. Maximal effects were observed with 1 x 10(-7) mol/L LTC4 or with 3 x 10(-7) mol/L LTD4. At these concentrations LTC4 and LTD4 induced the indicated increases above the responses to the following prestimulants (= 100%): 10(-4) mol/L histamine (71% and 74%, respectively), 10(-5) mol/L forskolin (54% and 106%), 10(-4) mol/L dibutyryl cyclic adenosine monophosphate (34% and 81%), and 10(-4) mol/L carbamylcholine (160% and 116%). Yet, adenosine triphosphate (2.5-5 x 10(-3) mol/L)-induced [14C]aminopyrine uptake in digitonin-permeabilized parietal cells was not further increased by LTC4 or LTD4. At 10(-5) mol/L the selective LTD4 antagonist L-660,711 (MK-571) reduced the effect of 3 x 10(-7) mol/L LTD4 by 74% but had no effect on the potentiation by LTC4. We conclude that the sulfidopeptide LTs C4 and D4, but not LTB4, exert a direct effect on rat parietal cells, and that this effect seems to be mediated by separate specific receptors. Leukotriene C4 and LTD4 potentiate prestimulated H+ formation by interacting with an intracellular mechanism that is commonly activated upon occupation of histamine H2- as well as muscarinic receptors, and that is also activated by the postreceptor stimuli forskolin and dibutyryl cyclic adenosine monophosphate; yet, this mechanism seems to be localized proximal to the H+,K+-adenosine triphosphatase.