Sensory irritation effects of methyl ethyl ketone and its receptor activation mechanism

The burning and painful effect in nose and eyes, termed sensory irritation, of methyl ethyl ketone vapours was investigated in a mouse bioassay. Sensory irritation is mediated via the trigeminal nerves and results in a reflexively induced decrease in respiratory rate in mice. Methyl ethyl ketone was used as a model substance for ketones. At the lower exposure concentrations a partial fading (desensitization) of the response was seen. Little desensitization was seen at higher concentrations. n-Propanol, a model substance for alcohols, desensitized the receptor at all exposure levels. Preexposure to propanol did not influence the response at high methylethyl ketone concentrations. This suggests that the two substances bind to different receptive sites with different properties, if the ketone response is due to a high exposure concentration. A decrease in tidal volume was also mediated from the upper respiratory tract. The tidal volume effect is mediated by nerves different from those mediating the frequency response, as the time-response relationship, the desensitization pattern, the maximum response and the apparent dissociation constants were different for the two types of effect. Neither the location nor the perceived response related to the volume response is known.