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Biomedical subjects

M A Reilly

Publications and source records attributed to M A Reilly.

12 recordsLinked to original sources

Age-related differences in response programming.

Age-related differential effects on reaction time (RT) performance for movement complexity and response-response (R-R) compatibility were examined in children, adolescents, and young adults. A two-choice RT paradigm involved three different finger responses, and each finger movement response was paired with every other movement response. Movement complexity was manipulated by varying the digits activated and was measured as the mean RT for a particular movement across all choice pairs. R-R compatibility was manipulated by altering the pairing of choice alternatives and was determined by the mean RT comparison for each of the movements according to the paired choice alternative. Simple RTs were also obtained for all finger movement responses for comparison with the RTs achieved in choice situations. Age-related differences were found for both movement complexity and R-R compatibility. Mean RT and response consistency improved with age. Although higher overall speeds were found with age, adolescents were not significantly slower than young adults. Adolescents did, however, make significantly fewer response errors on movements differing in complexity. Bilateral versus unilateral control and number of fingers involved in the task were found to affect both movement complexity and the compatibility between response pairs. The relationship between the alternative and choice response was found to be a robust factor affecting R-R compatibility. Choice responses were significantly slower than simple responses, and the rank ordering of movement responses was identical within the two paradigms.

Adolescent

Chronic nicotine administration increases binding of [3H]domperidone in rat nucleus accumbens.

An apparent inverse relationship between smoking and Parkinson's disease prompted an investigation of the effect of chronic nicotine administration on dopaminergic and serotonergic receptors in rat brain. Nicotine, 0.8 mg/kg, was injected once daily, five times per week, for 6 weeks. In nucleus accumbens the Kd for [3H]domperidone was increased 2-4-fold, and the Bmax was increased 1.5-2-fold. No changes were observed in the binding of [3H]domperidone in caudate-putamen or in that of [3H]ketanserin in frontal cortex. It is concluded that chronic nicotine administration may have a suppressant effect on central nervous system release of dopamine that in pre-parkinsonian persons causes an aversion to the effects of smoking.

Animals

Effect of histamine methylation inhibitors on entry of 14C-histamine into brain.

Pretreatment of mice, rats and guinea pigs with inhibitors of histamine methylation, followed by systemic injection of 14C-histamine, results in a significant increase in brain 14C-histamine relative to controls. It is suggested that the histamine methylating enzyme participates in the blood-brain barrier to histamine.

Amodiaquine

Effects of various S-adenosylmethionine preparations on histamine methylation in vitro and in vivo.

To test possible enhancement of in vivo methylation of histamine, mice were injected with S-adenosylmethionine (SAM) of approximately 96% purity. Instead of the expected enhancement, very strong inhibition of methylation was observed. Tests indicated that S-adenosylhomocysteine (SAH) probably was not the inhibitor. Pure SAM, from another source, showed no inhibition of methylation in rats and guinea pigs, and only slight inhibition in mice. Pure SAM was much more effective than the 96% SAM for histamine methylation in vitro. It seems either that injected SAM cannot enter cells containing the histamine methylating enzyme (HME), or that the endogenous supply of SAM is optimal. The inhibitor may be structurally related to SAM, possibly a by-product of SAM synthesis. As it is very effective even in the presence of large amounts of SAM, in pure form it would probably be the most potent inhibitor of histamine methylation available.

Animals

Methyl derivatives of histamine; interaction with histamine metabolism.

Several histamine analogs, with ring or side chain methyl groups, were tested for interaction with certain aspects of 14C-histamine metabolism. The physiological catabolite, denoted as 3-methylhistamine under the nomenclature we have adopted, is known to inhibit histamine methylation in vitro and in vivo. At low concentrations, all analogs inhibited histamine methylation by mouse brain homogenates; however 3-methylhistamine was completely ineffective against the highly active enzyme from rat didney, while 2-methylhistamine was most effective. None of the drugs showed a significant effect on in vivo formation of 14C-histamine by mouse stomach. All analogs had a definite effect on the distribution and fate of intravenously injected 14C-histamine. The 2-methyl analog was the strongest in vivo inhibitor of histamine methylation, and 3-methylhistamine next. The side chain N-methylated histamies altered uptake of 14C-histamine in some tissues but inhibited methylation weakly, if at all. Data on blood kidney and urine for 4-methylhistamine were unique, and suggested some effect on tubular reabsorption. 2-methylhistamine may prove to be the inhibitor of choice for in vivo studies on histamine methylation.

Animals

Activity changes in mouse brain histidine decarboxylase.

Mice were tested for effects of various factors on histidine decarboxylase of whole brain, or major brain regions. Factors included age, sex, fasting and feeding, season of year, time of day, freezing for various time intervals, and intracerebral injection of protein synthesis inhibitors daily for 2-5 days. In the latter test, 5 day treatment with acetoxycycloheximide reduced brain histidine decarboxylase activity. In one experiment, in which a marked activity increase was observed, brain infection seemed to be the stimulus. Brain enzyme activity in normal mice showed large fluctuations over periods of several months to one year; presumably this is of some physiological significance but the causes are obscure.

Age Factors

Comparison of in vitro and in vivo histamine methylation by tissues.

A method for determining the histamine-methylating enzyme (HME) using crude enzyme, and minute quantities of the substrate, was applied to tissues of mice, guinea-pigs and rats. Since high levels of endogenous histamine can affect the results, tissue homogenates were dialyzed prior to incubation. Findings were compared with in vivo data on methylating ability of individual tissues; most of this in vivo data is published but a new test of guinea-pig tissues was made using amodiaquine as an inhibitor. The correlation was good, better than that obtained by other procedures. It was observed that dialysis caused an increase in HME for some guinea-pig tissues, but a loss for some mouse tissues. Possible explanations are considered. Quinacrine N-mustard, a derivative of a known HME inhibitor, was tested in mice; it altered the distribution of injected 14C-histamine but showed no evidence of HME inhibition.

Amodiaquine