Histamine release from isolated rat mast cells induced by opiates: effect of sterical configuration and calcium

Abstract

The stereospecificity of the action of opiates on rat mast cells was investigated by means of the l- and d-isomers levorphanol and dextrorphan. The dose-response curves for histamine release induced by the 2 drugs were of a similar shape with a maximum at 2 X 10(-3) M and a pronounced minimum at 5 X 10(-3) M. At concentrations below 5 X 10(-3) M the effect of both drugs resembled that of morphine, i.e. the release occurred rapidly and inhibition was observed with naloxone, codeine, and antimycin A. Levorphanol, dextrorphan, and the antagonist levallorphan at concentrations above 5 X 10(-3) M seemed to be toxic to mast cells. The uptake of 45Ca in connection with histamine release induced by pethidine, levorphanol, and dextrorphan was lower than that of control cells, whereas the uptake induced by morphine did not differ from that of controls. The inhibition of compound 48/80-induced histamine release by morphine was paralleled by a reduced 45Ca uptake. The time course for the inhibitory effect of preincubation with morphine was similar for the histamine released induced by morphine and by compound 48/80. Washing of the cells after preincubation with morphine was without effect on the inhibition of morphine-induced histamine release, whereas the inhibition of compound 48/80 was reduced. The present observation with morphine and compound 48/80 support our previous impression of similarities in their mode of action, but a mechanism implying an interference by morphine with the disposition of calcium could also account for the findings. The observed antagonism between morphine and calcium resembles that of opiate receptors, but histamine release induced by opiates does not involve stereospecific opiate receptors.

Functional differences between human cutaneous mast cells and basophils: a comparison of morphine-induced histamine release

“…Our results confirm the requirement for a divalent cation. While GROSMAN [17] noted an inverse relationship between calcium concentration and histamine release, we found a direct relationship. However, this must be qualified as Grosman's experiments involved rat mast cells and extremely high opiate concentrations.…”

Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals

“…Residential mast cells and circulating basophils [41,42] are the source of the released histamine. Morphine releases histamine in dogs from the same stores as compound 48/80 [42], and from isolated purified rat and human mast cells in vitro [43][44][45][46]. The mast cell histamine release by narcotics is selective and non-cytotoxic [43], and possibly entails the presence of specific opiod receptors since the release of histamine is 128 Ⅵ blocked by naloxone [44].…”

Alfentanil: Correlations Between Absence of Effect Upon Subcutaneous Mast Cells and Absence of Granuloma Formation After Intrathecal Infusion in the Dog

“…An interesting consideration that we entertained was that the opioid effects on mast cells paralleled this profile. It has been long appreciated that agents such as morphine, but not fentanyl, degranulate mast cells (10)(11)(12)(13)(14); and this effect is not considered to be reversed by naloxone (15,16). We note that degranulation of mast cells by some but not all opiates and the absence of antagonist sensitivity provides an intriguing link.…”