ABSTRACT
Selective release of histamine from rat peritoneal mast cells in vitro was induced by compound 48/80 (1 microgram/ml). Most of the release (75-80%) occurred in a calcium(Ca)-free medium but optimum release was obtained in the presence of 0.9 mM Ca. The release in Ca-free medium still occurred after 180 min incubation. However, prolonged incubation (180 min) in a medium containing chelating agents (EDTA or EGTA) resulted in complete inhibition of histamine release, loss of fluorescence seen with chlortetracycline (CTC) and loss of previously loaded 45Ca from the mast cells. Addition of Ca to these cells resulted in rapid restoration of fluorescence with chlortetracycline. There was also a rapid uptake of 45Ca. Partial depletion of cellular Ca (60 min incubation with EDTA) reduced the rate as well as the amount of histamine release by compound 48/80. These data provide direct evidence for the depletion of cellular Ca which is utilized by compound 48/80 to induce histamine release.
Subject(s)
Calcium/metabolism , Chlortetracycline/pharmacology , Histamine Release/drug effects , p-Methoxy-N-methylphenethylamine/pharmacology , Animals , Calcium Radioisotopes , Edetic Acid/pharmacology , Egtazic Acid/pharmacology , Male , Mast Cells/metabolism , Rats , Time FactorsSubject(s)
Muscles/blood supply , Receptors, Adrenergic, beta/physiology , Receptors, Adrenergic/physiology , Animals , Blood Pressure/drug effects , Dogs , Epinephrine/pharmacology , Female , Femoral Artery/physiology , Heart Rate/drug effects , Isoproterenol/pharmacology , Male , Myocardial Contraction/drug effects , Norepinephrine/pharmacology , Vasoconstriction/drug effectsABSTRACT
A substituted acridone, 10-(2-dimethylaminopropyl)-9-acridone HCl (M-129), was taken up by isolated rat peritoneal and pleural mast cells in direct relationship to the degree of selective histamine release induced by compound 48/80. Other selective releasing agents, i.e., polymyxin B and anti-rat mast cell serum, also augmented uptake of M-129. Augmented uptake of M-129 was inhibited by measures that inhibited selective histamine release, i.e., cold, brief heating of the mast cells, N-ethylmaleimide and ninhydrin. 48/80 did not agument uptake of M-129 in rat erythrocytes or in rat serous fluid cells from which mast cells had been removed. M-129 taken up by mast cells was readily removed by two to three washes. Augmented uptake induced by 48/80 was specific for M-129 and acridone itself. Related compounds, i.e., a quaternary acridone derivative [10-(2-triethylaminoethyl)-9-acridone iodide] (M-231), acridine and acridan did not show augmented uptake. There was no relationship between heptane-water partition coefficients and uptake. It is postulated, based on estimates of cell membrane area, that M-129 is loosely bound to plasma membrane and that the augmented uptake associated with selective histamine release from rat mast cells is due to expanded plasma membrane that results from irreversible or slowly reversible exocytosis.
