Publications

Concanavalin A- (con A) induced release of histamine from normal rat mast cells was studied. In the presence of phosphatidylserine (PS) con A induced a concentration and temperature-dependent, noncytotoxic histamine release at con A concentrations ranging from 0.1 to 100 mug/ml. The optimal con A concentration, 100 mug/ml, caused a 27.3% (+/- 2.7 S.E.M.) net histamine release. Release began approximately 30 sec after addition of con A and was complete within 45 min. In the absence of PS, no net con A-induced release occurred. The effect of PS was concentration dependent from 1 to 100 mgg/ml. PS alone, however, did not cause histamine release. Binding studies indicated that mast cells bound up to 16 X 10(6) con A molecules per cell without histamine release. Upon removal of unbound con A and the addition of PS, normal histamine release occurred. Alpha-Methyl-D-mannose (50 mM) prevented both con A binding and histamine release and if added after Con A, caused a rapid cessation of histamine release and a reversal of con A binding. This study indicates several important advantages of the con A-induced histamine release system. Binding of con A to mast cells can be dissociated from histamine release by omitting PS from the medium. Release can then be induced by the addition of PS. Alpha-Methyl-D-mannose can be used to terminate rapidly the ongoing release reaction at any phase of the interaction. This system is potentially very useful for investigation of metabolic events during histamine release.

The effects of oral propranolol were evaluated in 10 normal volunteers. The resting heart rate decreased from the mean control value of 68 plus or minus 3.3 (SE) to 56 plus or minus 2.8 beats per minute (bpm) on propranolol (p smaller than 0.001, paired test). Mean systolic blood pressur also decreased from 125 plus or minus 5.0 to 114 plus or minus 4.2 mm Hg (p smaller than 0.03). Resting systolic time intervals were unaffected by propranolol. Mean maximal treadmill exercise tolerance time was not significantly altered by propranolol although the mean heart rate systolic blood pressure product a maximal exertion was markedly decreased (1.91 plus or minus 0.17 vs 2.62 plus or minus 0.17 times 10-4, p smaller than 0.004) . The nonsignificant effect of oral propranolol on resting systolic time intervals and maximum exercise tolerance despite significant changes in heart rate and blood pressure at rest and duringexercise stand in contrast to the reported effects of intravenous propranolol. Explantations for this difference between the effects of oral and intravenous propranolol in normal subjects are examined.