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B Crowell

Publications and source records attributed to B Crowell.

26 records · Page 2Linked to original sources
PubMed1993

The effects of L-dopa on the activity of methionine adenosyltransferase: relevance to L-dopa therapy and tolerance.

L-dopa, the major treatment for Parkinson's disease (PD), depletes S-adenosyl-L-methionine (SAM). Since SAM causes PD-like symptoms in rodents, the decreased efficacy of chronic L-dopa administered to PD patients may result from a rebound increase in SAM via methionine adenosyl transferase (MAT), which produces SAM from methionine and ATP. This was tested by administering intraperitoneally saline, or L-dopa to mice and assaying for brain MAT activity. As compared to controls, L-dopa (100 mg/kg) treatments of 1 and 2 times per day for 4 days did not significantly increase MAT activity. However, treatments of 3 times per day for 4 and 8 days did significantly increase the activity of MAT by 21.38% and 28.37%, respectively. These results show that short interval, chronic L-dopa treatments significantly increases MAT activity, which increases the production of SAM. SAM may physiologically antagonize the effects of L-dopa and biochemically decrease the concentrations of L-dopa and dopamine. Thus, an increase in MAT may be related to the decreased efficacy of chronic L-dopa therapy in PD.

Adenosine Triphosphate↗
PubMed1992

Parkinson's disease-like effects of S-adenosyl-L-methionine: effects of L-dopa.

The major symptoms of Parkinson's disease (PD) are due to degeneration of the nigrostriatal pathway and depletion of dopamine (DA). Tyrosine hydroxylase (TH), norepinephrine (NE), serotonin (5-HT), and melanin pigments are also decreased and acetylcholinergic activity increased. Biochemically, increased methylation can cause the depletion of DA, NE, 5-HT, and melanin pigments and also an increase of acetylcholine; thus, increased methylation can present a biochemical picture that resembles the biochemical changes that occur in PD. During the therapy of PD with L-dopa, it is well known that L-dopa reacts avidly with S-adenosyl-L-methionine (SAM), the biologic methyl donor, to produce 3-O-methyl-dopa. Correspondingly, L-dopa has been shown to deplete the concentration of SAM, and SAM has been found to induce PD-like motor impairments in rodents; therefore, an excess of SAM-dependent methylation may be associated with Parkinsonism. To further study the effects of methylation, SAM was injected into the lateral ventricle of rats. SAM caused tremors, rigidity, abnormal posture, and dose-related hypokinesia. Doses of 9.38, 50, and 400 nM/rat caused 61.9, 73.4, and 94.8% reduction, respectively, of motor activity. A 200-mg/kg IP dose of L-dopa, given before 50 nM SAM, blocked the SAM-induced hypokinesia. SAM also caused a decrease in TH immunoreactivity, apparent degeneration of TH-containing fibers, loss of neurons, and the accumulation of phagocytic cells in the substantia nigra. These results showed that excess SAM in the brain, probably due to its ability to increase methylation, can induce symptoms that resemble some of the changes that occur in PD.

Animals↗
PubMed1988

Identification of motor neurons for accessory muscles of inspiration and expiration, pectoralis, trapezius and external oblique: comparison with non-respiratory skeletal muscle.

The motor neurons for the accessory muscles of respiration, pectoralis, trapezius, external oblique, and the rectus abdominis were studied in the spinal cord. The objective was to determine if the localization and morphology of the motor neurons for these muscles bear any distinct relationship to the specialized function of these muscles, serving both as supportive skeletal muscles and as accessory respiratory muscles. In addition, it was of interest to know if the inspiratory role of the pectoralis and trapezius muscles and the expiratory role of the external oblique and rectus abdominis are related to the spatial organization of the motor neurons; this knowledge may be important in the discrimination of influences from afferent connections. The motor neurons for these muscles were retrogradely labeled with true blue and were compared with the triceps motor neurons. All neurons occurred ipsilateral and most labeling occurred in C6-7. The motor neurons for the accessory muscles were mainly confined to the ventrolateral tip of the ventral gray matter. The triceps neurons were dorsolateral to the respiratory related neurons in C6-7. Within the confines of the ventrolateral area, the majority of neurons for the pectoralis were localized medial to ventromedial, those for the trapezius were ventrolateral, and those for the external oblique were in the extreme ventrolateral to ventral sections of C7. No neurons were observed in C2 to T2 for the rectus abdominis. A second neuronal column occurred medioventrally in the ventral gray of C4-6 for the trapezius, and is distinct and separated from the C6-7 cell column.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗