Histamine release from isolated rat mast cells: effect of morphine and related drugs and their interaction with compound 48/80.

Morphine, codeine, and pethidine induced histamine release from isolated rat mast cells in the same concentration range. The histamine release induced by morphine and by codeine occurred rapidly, in contrast to the release induced by pethidine. The effect of morphine was reduced by the presence of calcium, enhanced by magnesium, and unaffected by phosphatidyl serine. Pretreatment of the cells with the ionophore A23187 inhibited the response to morphine, indicating a requirement for intracellular calcium. The release induced by morphine and by codeine was inhibited by antimycin A, but the release induced by pethidine was unaffected. The effect of morphine was inhibited by both naloxone and codeine, and naloxone also reduced the release induced by codeine. The effect of pethidine was inhibited by codeine, whereas the influence of naloxone was less pronounced. Preincubation of cells with lower concentrations of morphine reduced the response to a subsequent exposure to morphine. The release induced by compound 48/80 was similarly inhibited after preincubation with morphine as well as after preincubation with codeine and with pethidine. In contrast, preincubation with pethidine enhanced the effect of subsequent incubation with pethidine. Preincubation with low concentrations of compound 48/80 reduced the response to compound 48/80 in the absence of calcium, but was without effect in the presence of calcium. It is suggested that morphine, codeine, pethidine, and naloxone act on common or closely relates sites on the mast cell and that these sites may account for the action of compound 48/80 as well. The results indicate similar mechanisms for the histamine release induced by morphine and by codeine, whereas pethidine clearly has a different mode of action.