Reference

Biopterin synthesis defect

Biopterin synthesis defect. Treatment with L-dopa and 5-hydroxytryptophan compared with therapy with a tetrahydropterin. McInnes, Roderick R.; Kaufman, Seymour; Warsh, Jerry J.; Van Loon, Glen R.; Milstien, Sheldon; Kapatos, Gregory; Soldin, Steven; Walsh, Peter; MacGregor, Daune; Hanley, W. B. (Dep. Genet. Pediatr., Hosp. Sick Children, Toronto, ON M5G 1X8, Can.). J. Clin. Invest., 73(2), 458-69 (English) 1984. CODEN: JCINAO. ISSN: 0021-9738. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2, 14 A generalized deficiency of monoamine neurotransmitters in a patient with a defect in biopterin [22150-76-1] synthesis was identified. Neurotransmitter precursors L-dopa [59-92-7]; 5-hydroxytryptophan (5-HTP) [56-69-9] and a tetrahydropterin 6-methyltetrahydropterin (6MPH4) [942-41-6] were investigated for their ability to normalize monoamine neurotransmitter metab. Before treatment, the concns. of dopamine (DA) [51-61-6], norepinephrine [51-41-2], epinephrine [51-43-4] and 6 monoamine metabolites were very low or undetectable in plasma,, cerebrospinal fluid, or urine. L-Dopa and 5-HTP replacement was started at 7 mo. This therapy generally cor. the deficiency of monoamines and their metabolites, and improved neurol. development until the age of 25 mo. Despite these benefits, the intermittent administration of L-dopa could not produce a stable improvement of acute neurol. function or DA metab. In the 3 h after L-dopa administration, plasma DA and the motor activity and alertness of the patient rose and fell in parallel. Doses of L-dopa that were clin. optimal produced normal plasma levels of norepinephrine and epinephrine, but excessive concns. of DA and its metabolites. Furthermore, the clin. and biochem. effects of L-dopa were inhibited by phenylalanine and 5-HTP, resp., demonstrating that these amino acids have antagonistic pharmacol. effects. Physiol.In this experiment, several chemicals are used like 59-92-7 and 942-41-6 correction of the monoamine deficit and the hyperphenylalaninemia of this disorder was attempted at age 35 mo using high doses (8-38 mg/kg/day) of 6MPH4 which controlled the hyperphenylalaninemia. Significant concns. of 6MPH4 were obtained in the cerebrospinal fluid; no neurol. improvement or stimulation of monoamine synthesis in the central nervous system was detected. These findings indicate that complexity in replacement therapy with L-dopa and 5-HTP, but suggest that this treatment may be partially effective in biopterin-deficient patients who are unresponsive to high doses of tetrahydropterins. .

Effects of castration and adrenalectomy on in vitro rates of tryptophan hydroxylation and levels of serotonin in microdissected brain nuclei of adult male rats

Effects of castration and adrenalectomy on in vitro rates of tryptophan hydroxylation and levels of serotonin in microdissected brain nuclei of adult male rats. Long, J. B.; Youngblood, W. W.; Kizer, J. S. (Sch. Med., Univ. North Carolina, Chapel Hill, NC 27514, USA). Brain Res., 277(2), 289-97 (English) 1983. CODEN: BRREAP. ISSN: 0006-8993. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) Rates of 5-HTP [56-69-9] synthesis and levels of 5-HT [50-67-9] were measured in microdissected brain nuclei following castration or adrenalectomy of adult male rats. Fourteen days following gonadectomy, 5-HTP synthesis decrease in the nucleus raphe dorsalis (DR) and nucleus centralis superior (NCS), whereas levels of 5-HT were unchanged in the 7 brain nuclei examd. Administration of testosterone [58-22-0] to castrated rats not only did not reverse the castration-induced decrease in 5-HTP synthesis in the DR and NCS, but also decreased 5-HT synthesis in the nucleus amygdaloideus centralis (AGC) and the nucleus septalis lateralis (LS). Following administration of testosterone, 5-HT levels were unchanged. Ten days following bilateral adrenalectomy, 5-HTP synthesis increased in the NCS and the median eminence. 58-22-0 and 50-67-9 are also in the experiment. Levels of 5-HT increased only in the median eminence. The increased 5-HTP synthesis and 5-HT levels following adrenalectomy were not reversed by corticosterone administration. These selective changes in 5-HT metab. did not result from hormonal effects on the availability of tryptophan to the brain. Apparently, there are subsets of serotonergic neurons in the rat central nervous system which respond uniquely to removal of the gonads and adrenals. The dissocn. between serum and brain tryptophan concns. and change in rates of 5-HTP synthesis argue against tryptophan availability as being a primary determinant of 5-HT biosynthesis and for a direct endocrine central nervous system interaction with serotonergic neurons. .