[Histamine release due to ganglion blocking agent and muscle relaxants from rat mast cells]

The mechanisms of histamine release due to d-tubocurarine from rat mast cells have long been known to anesthesiologists, such as degranulatory process, Ca++ dependent process and energy coupled process. However, not much is known about histamine release due to some drugs such as trimethaphan and muscle relaxants other than d-tubocurarine, like alcuronium, pancuronium or succinylcholine, although many clinical reports related to hypersensitivity reactions due to muscle relaxants can be found. In this experiment, the histamine releasing activities of trimethaphan and muscle relaxants were examined using the laboratory model created by Ellis (1970) who reported the selective release of histamine due to d-tubocurarine. Also observed the effects of autonomic neuro-effective drugs such as theophylline, isoproterenol or carbamylcholine on histamine release due to d-tubocurarine. From this experiment, it is suggested that trimethaphan releases histamine through nonselective process but muscle relaxants release histamine selectively. It is also found that pancuronium had little effects on rat mast cells and its histamine releasing activity was selective, if any. Histamine release from rat mast cells due to d-tubocurarine was clearly depressed by pretreatment of theophylline or isoproterenol. In the case of carbamylcholine, low doses inhibited histamine release, but higher doses allowed histamine to be liberated from mast cells. From these findings, it is concluded that some drugs like theophylline or isoproterenol may diminish the side effects of d-tubocurarine and perhaps some other muscle relaxants. Also, as theophylline and isoproterenol are concerned, increase of cyclic AMP may play a role in the inhibition of histamine release. The data using carbamylcholine suggested that the cholinergic receptors on the rat mast cells may be involved through the process of histamine release.