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Biomedical subjects

G H Dodd

Publications and source records attributed to G H Dodd.

At least 19 recordsLinked to original sources
PubMed1996

The lipid membrane hypothesis of schizophrenia: implications for possible clinical breath tests.

The diagnosis of disease on the basis of an altered profile of breath volatiles is a new area of clinical biochemistry. The membrane hypothesis of schizophrenia leads to a number of predictions about possible volatile biochemical markers for this condition. These molecules would arise from autoxidation of arachidonic acid and possibly other unsaturated fatty acids. Preliminary experimental studies in this area are reviewed. The results are encouraging and developments in analytical methodology, especially mass spectrometry and electronic nose technology, hold promise for an objective test for monitoring the progress of the disease and possibly for diagnosis.

Biomarkers↗
PubMed1989

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.

Alkanes↗
PubMed1989

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.

Adenylyl Cyclases↗
PubMed1989

Characterization of the total lipid and fatty acid composition of rat olfactory mucosa.

Phospholipid accounted for 81% (by weight) of the total lipid of rat olfactory mucosa. Phosphatidylcholine (46% of total phospholipids) and phosphatidylethanolamine (26%) were the predominant phospholipids. Phosphatidylinositol (8%), sphingomyelin (6%), and phosphatidylserine (7%) were the next most abundant phospholipids, with cardiolipin (4%) and phosphatidic acid (1%) present in lesser amounts. Only trace amounts of the polyphosphoinositides, phosphatidylinositol monophosphate, and phosphatidylinositol bisphosphate were detected. Sterol was the major neutral lipid present (83% of the total neutral lipid mass) with lesser amounts of triacylglycerols (7%), steryl esters (6%), free fatty acids (4%), and diacylglycerols (1%). Monoacylglycerols were detected only in trace amounts. The sterol to phospholipid ratio was 0.39:1. Most of the phospholipids of the olfactory mucosa showed a high polyunsaturated fatty acid content, with the arachidonic acid (20:4) and docosahexaenoic acid (22:6) residues predominating. The fatty acids in sphingomyelin, however, were almost totally saturated and included the 24:0 and 24:1 residues, which were not detected in other phospholipids. Polyunsaturated fatty acids accounted for less than 25% of the total fatty acid of any individual neutral lipid and comprised largely linoleic and arachidonic acids. The results are discussed in relation to the putative role of lipids in olfactory signal transduction.

Animals↗
PubMed1988

Spatial variation in response to odorants on the rat olfactory epithelium.

We have measured the electro-olfactogram produced by four odorants, nicotine, i-pentyl acetate, i-pentanoic acid and cineole from twelve positions on an in vitro preparation of rat olfactory tissue. Each odorant shows a different pattern of response over the twelve positions which can be explained by differences in olfactory receptor populations between regions of the rat olfactory epithelium. The result for nicotine is further evidence that there are olfactory receptors which are stimulated by nicotine when it is presented as a vapour.

Action Potentials↗
PubMed1988

Xenobiotic metabolism in the nasal epithelia.

The nasal epithelia in several species contains fairly high levels of drug metabolising enzymes, and in many cases the site specific toxicities of chemicals are due to their metabolic activation in the nasal tissues. This article reviews some of the current literature on the metabolic capacities of nasal epithelia, in particular the distribution and characteristics of cytochrome P-450 isozymes. In addition to the role of these nasal enzymes in metabolism of inhaled xenobiotics, other possible biological roles for these enzymes are also discussed.

Animals↗
PubMed1987

Binding of aromatic isonitriles to haemoglobin and myoglobin.

A series of aromatic isonitriles were synthesized and their binding to sheep haemoglobin and horse heart myoglobin was investigated. The disubstituted ligands 2,6-dimethylphenylisonitrile and 2,6-diethylphenylisonitrile were found to bind to horse-heart myoglobin with affinities ranging from 500 to 5000 times greater than that of ethylisonitrile (4.6 x 10(-6) M) which has been the tightest binding isonitrile ligand for myoglobin thus far reported. The tight binding was not found to vary significantly with pH or temperature. An explanation for the unexpectedly high affinity is offered in terms of the electronic structure of aromatic isonitriles.

Binding Sites↗
PubMed1987

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.

Animals↗
PubMed1987

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.

Adenylyl Cyclases↗
PubMed1987

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.

Animals↗
PubMed1987

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.

Animals↗
PubMed1986

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.

Acetophenones↗
PubMed1983

Chemical-modification studies on rat olfactory mucosa using a thiol-specific reagent and enzymatic iodination.

1. A rat olfactory preparation, suitable for biochemical studies in vitro on olfactory mechanisms, is described. 2. The effects of the impermeant chemical modification reagents mersalyl (a thiol reagent) and enzymatic iodination, on the amplitude of the electroolfactogram (EOG) responses elicited from rat olfactory mucosa by pulses of odorant vapours was studied using 12 odorants differing widely in odour quality and molecular structure: amyl acetate, carvone, decanal, butylamine, cineole, citronellol, cresol, diacetyl, dimethylethyl-pyrazine, naphthalene, octanethiol and valeric acid. 3. Both reagents irreversibly reduced the EOG amplitude to all odorants to an extent dependent on the reagent concentration. Two subpopulations of animal preparations could be distinguished on the basis of the extent to which they survived the iodination whereas mersalyl appeared to sample a single population of preparations. 4. Small but statistically significant differences were observed between the responses of each odorant with each reagent but no simple correlation between either the molecular structure or odour quality of the odorants and the reagent effect is apparent for the case of mersalyl. With iodination the responses from the three flexible-aliphatic-chain odorants were reduced to a greater extent than the other odorants, all of which had a dissimilar molecular structure. 5. The ability of three odorants, amyl acetate, carvone and decanal, to protect the receptors for the odorants against chemical modification was investigated. The protecting odorants were applied directly to the mucosa as a dilute solution in Ringer's medium. No specific odorant protection effects were observed. 6. The results are discussed in relation to a model of the olfactory mechanism involving relatively non-specific receptor proteins. Each receptor type is envisaged as interacting weakly with a number of odorants and each odorant interacts with a number of receptors.

Aldehydes↗
PubMed1978

Bovine olfactory and nasal respiratory epithelium surfaces. High-voltage and scanning electron microscopy, and cryo-ultramicrotomy.

High-voltage transmission electron microscopy and cryo-ultramicrotomy together with scanning electron microscopy and some conventional transmission electron microscopy of ultrathin sections have been applied to the mucous surfaces of bovine olfactory and respiratory epithelia. Distal segments of olfactory cilia tend to run in parallel and could be followed over distances up to about 30 micrometer using high-voltage electron microscopy. This technique and scanning electron microscopy showed that on average 12--13 of such cilia could be observed per nerve ending. After correction for obscured cilia this number becomes about 17. High-voltage micrographs and micrographs made from sections prepared with a cryo-ultramicrotome showed the presence of electron-lucent pockets inside the olfactory mucus. The latter technique also showed that the mucus itself is not fibrous, but rather a continuum varying in electron density. The mucus layer contains various granular structures. Ciliary and microvillar membranes appear thicker with cryo-ultramicrotomy than when the sections are prepared with conventional techniques. The cores of the axonemal microtubules in olfactory as well as in respiratory cilia are darkly stained with this technique. Vesicles present inside the nerve endings are also darkly stained. Dimensions and some other numerical values of interest in olfaction are presented.

Animals↗