Biomedical subjects
S G Shirley
Publications and source records attributed to S G Shirley.
Concanavalin A reveals olfactory receptors which discriminate between alkane odorants on the basis of size.
For certain odorants, the amplitude of the rat electro-olfactogram is reduced if the olfactory epithelium is treated with the lectin concanavalin A. When normal and cycloalkanes of one to ten carbon atoms are used as odorants at equimolar concentration, the maximum reduction in amplitude is found to correlate with the size of the stimulus molecule. This observation is consistent with the notion that concanavalin A disables an olfactory receptor molecule which normally responds to the alkyl moiety of odorants in a particular size range. That moiety may thus represent a 'primary' quality-determining component in odour discrimination.
The detergent Solulan C-24 reveals properties of the olfactory adenylate cyclase system.
The detergent Solulan C-24 has been shown to activate the olfactory adenylate cyclase, with loss of the odorant modulation, at concentrations too low to cause significant solubilization. The activation is synergistic with that of nonhydrolysable GTP analogues, forskolin and AlF4-. These effects are not reversible. Solulan causes the cyclase activity to become subject to ATP inhibition, which is competitively relieved by GTP gamma S, and increases the GTP gamma S concentration required for half-maximal stimulation of the system. This suggests a change in the GTP-binding site of the stimulatory G-protein. Activation by GTP gamma S, without Solulan, indicates that the cyclase catalytic unit, rather than the available G-protein, may be limiting in the system. We suggest that Solulan may remove an inhibitory control on the cyclase activity.
Are we really studying olfactory transduction?
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Evidence for an olfactory receptor which responds to nicotine--nicotine as an odorant.
The tobacco alkaloid (S)(-)-nicotine, when applied as a vapour to an in vitro head preparation, stimulates the olfactory epithelium in three strains of rats and to a lesser extent in two strains of mice. The electro-olfactogram (EOG) generated by nicotine has similar characteristics to the EOGs produced by known odorants. The nicotine EOG increases with increasing concentration of nicotine vapour (1-100 nM) applied to the olfactory epithelium. Differential reduction of the nicotine EOG by the lectin concanavalin A is seen in Wistar and Lister Hooded rats. The reduction of the nicotine EOG by concanavalin A is prevented by adding alpha-methyl-D-mannoside to the lectin superfusion medium. This suggests that there is a glyco-moiety associated with at least one olfactory receptor responding to nicotine. Our results suggest that rat olfactory epithelium has receptor sites for nicotine. Nicotine is an unusual compound because it shows both odorant and pharmacological properties.
The influence of temperature and membrane-fluidity changes on the olfactory adenylate cyclase of the rat.
At physiological temperatures, the activity of the olfactory adenylate cyclase of the rat is fairly insensitive to small changes in temperature. Membrane fluidization by benzyl alcohol also produces rather small modulations of cyclase activity, although this chemical also has a more specific effect on the enzyme. Insensitivity to temperature and membrane-fluidity changes are desirable properties for a transduction system which must function in an exposed environment.
The effect of concanavalin A on the rat electro-olfactogram. Differential inhibition of odorant response.
When the rat olfactory mucosa is treated with concanavalin A, it subsequently shows diminished sensitivity towards 60% of the 112 odorants tested (as judged by the amplitude of the electro-olfactogram response). Odorants containing four to six carbon atoms tend to show the largest (absolute) diminutions, suggesting a receptor for this kind of odorant, although the structural specificity is weak. The receptor seems to be of particular importance in the detection of thiols, carboxylic acids and hydrocarbons of the above size, since these compounds loose the highest proportion of their original signal. The concanavalin A appears to be binding to the glycan of one or more cell-surface proteins. The binding may be at, or close to, at least one odorant receptor.
The effect of concanavalin A on the rat electro-olfactogram at various odorant concentrations.
We have studied the effect of concanavalin A (Con A) on the rat electro-olfactogram response to several odorants. Each odorant was applied over a range of concentrations. For hydrophobic odorants whose response was affected by Con A, the diminution in response was maximal at odorant concentrations of about 1 microM in the olfactory mucus. The (odour) concentration-dependence of the change is compatible with the idea that Con A inactivates one or more types of olfactory receptor that normally bind odorants with dissociation constants of the order of 100 nM. With hydrophilic odorants we had to apply concentrations very much higher than this to elicit any response from the system. At these high concentrations we could observe Con A-induced diminutions in response.
Olfactory adenylate cyclase of the rat. Stimulation by odorants and inhibition by Ca2+.
Membranes prepared from the olfactory mucosa of the rat show a high level of adenylate cyclase activity. The activity increases up to 2-fold in the presence of physiologically relevant concentrations of odorants and is inhibited by Ca2+. The level of cyclase activity found is sufficient to explain the speed of olfactory transduction, which occurs on a time scale of tens of milliseconds.
Identification of skin in airborne particulate matter.
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