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Biomedical subjects

J D Pearson

Publications and source records attributed to J D Pearson.

At least 235 records · Page 13Linked to original sources
PubMed1975

The estimation of 3,4-dihydroxyphenylacetic acid, homovanillic acid and homo-isovanillic acid in nervous tissue by gas-liquid chromatography and electron capture detection.

1 A gas chromatographic method using electron capture detection is described for the estimation of three acidic metabolites of dopamine, 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid, HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-hydroxy-4-methoxyphenylacetic acid (homo-isovanillic acid, iso-HVA). The method is based on the formation of the trifluoroacetyl-hexafluoroisopropyl derivatives of the three acids. 2 The method has been applied to the estimation of DOPAC, HVA and iso-HVA in tissues from the central and peripheral nervous systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1974

Relationships between chemical structure and affinity for postganglionic acetylcholine receptors of the guinea-pig ileum.

1 Some phenylacetyl, diphenylacetyl, benziloyl and (+/-)-cyclohexylphenylglycolloyl esters have been made with 2- and 3-hydroxymethylpyrrolidines, 3-hydroxymethyl-N-methylpiperidine, piperidin-3-ols, piperidin-4-ols, 2,2,6,6-tetramethyl-N-methylpiperidin-4-ol, tropine, pseudotropine and quinuclidin-3-ol, and the affinity of these compounds and of their metho- and etho- derivatives has been measured for postganglionic acetylcholine receptors of the guinea-pig isolated ileum.2 Some of the compounds were very active indeed; the benziloyl esters of N-methylpiperidin-4-ol methiodide, tropine methiodide, and quinculidin-3-ol, and the (+/-)-cyclohexylphenylglycolloyl esters of N-methylpiperidin-4-ol and its methiodide had affinity constants greater than 10(10).3 The effects of inserting an additional methylene group onto the nitrogen were extremely variable, ranging from a decrease in log K of 1.64 units to an increase of 0.97 units. The effects of replacing hydrogen by phenyl in the acid portion ranged from an increase of 1.04 units to an increase of 3.06 units and of replacing hydrogen by hydroxyl from a decrease of 0.09 units to an increase of 1.94 units.4 The extent of the variation in the effects of a particular change in structure on affinity does not appear to be any different in these relatively rigid compounds from that observed with the same changes in open-chain aminoalcohols.5 Reasons for the variable effects of groups on affinity are discussed. If differences in effects on preferred conformations of these particular compounds in solution are of secondary importance, the effect of a group on affinity will be the net result of what it could contribute to binding, offset by the disturbance it causes to existing binding. The maximum effect observed in a large number of comparisons may indicate the contribution in the absence of disturbance and for groups containing only carbon and hydrogen it appears to be related to size, assessed from the increments in apparent molal volume at infinite dilution. The variation in the effects of these groups also appears to be related to size. Changes involving groups containing oxygen can produce bigger contributions to binding, and a bigger variation in contribution, than would be expected from their size.6 It is difficult to predict the extent to which groups may fail to produce their maximum effects. Variation is greatest with groups which could produce the biggest changes and so are of the greatest interest.7 The relevance of the results to the successful prediction of biological activity is discussed.

Acetylcholine↗
PubMed1972

A comparison of the affinities of antagonists for acetylcholine receptors in the ileum, bronchial muscle and iris of the guinea-pig.

1. Isolated preparations of bronchial strip and of intact iris from the guineapig have been adapted for the measurement of affinity constants of substances which block post-ganglionic acetylcholine receptors.2. The affinity constants of 28 compounds on bronchial muscle and of 8 compounds on the iris have been compared with values measured on the guinea-pig ileum.3. Although the compounds differed up to a million-fold in affinity, most of the estimates of log affinity constant for the bronchial muscle and iris differed only slightly from those on the ileum.4. Some of the differences could be attributed to the actions of hexamethonium, used in the tests on the ileum but not, initially, in the tests with the bronchial strip and iris. Hexamethonium reduced most of the estimates of log K for the receptors in the bronchial strip by a variable but significant amount, which could be due, at least in part, to a weak post-ganglionic blocking (atropine-like) action. On average, hexamethonium had little effect on the estimates made with the ileum, appreciably decreasing estimates with some compounds and increasing those with others.5. The results indicate that, although there may be differences between the acetylcholine receptors in the three types of tissue, there is no conclusive evidence, because the differences in affinity which we have observed could have arisen from differences in the experimental conditions. This is illustrated by results obtained with the guinea-pig ileum recorded with the same technique as was used for the bronchial strip, which are presented as an appendix.6. Such differences as may exist between these three types of acetylcholine receptor are likely to be limited to the replacement of one aminoacid in the receptor protein by a homologue.

Acetylcholine↗