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Biomedical subjects

G M Tyce

Publications and source records attributed to G M Tyce.

At least 127 records · Page 7Linked to original sources
PubMed1979

Effect of administration of 5-hydroxytryptophan and an inhibitor of L-aromatic amino acid decarboxylase on glucose metabolism in rat brain.

The effect of 5-hydroxytryptophan (5-HTP)--the precursor of serotonin (5-hydroxytryptamine, 5-HT)--and of an inhibitor, N-(DL-seryl)-N'-(2,3,4-trihydroxybenzyl)hydrazine (Ro4-4602), of L-aromatic amino acid decarboxylase on the metabolism of glucose to amino acids in brain tissue was investigated. Labeled glucose (20 muCi, 0.24 mg in 0.2 ml 0.9% saline) was injected intravenously into fed rats pretreated with Ro4-4602 (50 mg/kg intraperitoneally) either alone or in combination with 5-HTP (30 mg/kg intravenously) or with the appropriate vehicle. After the injection of Ro4-4602 plus 5-HTP, the concentrations of 5-HT and 5-HTP in brain were increased, but the increase of 5-HTP was more pronounced and prolonged than the increase in 5-HT. This suggested that Ro4-4602 slightly inhibits the reaction of decarboxylation in the brain, although at the dose used the drug is usually considered to act only peripherally. After administration of Ro4-4602 alone or combined with 5-HTP, the concentration of glucose in plasma was not significantly increased. However, the concentration of glucose in brain was markedly increased with such treatments. The administration of Ro4-4602 alone or combined with 5-HTP reduced the flux of 14C from labeled glucose to amino acids in brain. The concentrations of amino acids in brain were little changed by these treatments.

5-Hydroxytryptophan↗
PubMed1979

Pyridoxal 5'-phosphate levels in brain after treatments which impair cerebral glucose metabolism.

Pyridoxal 5'-phosphate (PLP) concentrations were measured in brains of rats to determine whether a deficiency of this coenzyme was a common feature in hepatic coma, ethanol intoxication, and in animals treated with L-dopa or with 5-hydroxytryptophan (5-HTP) alone or with inhibitors of MAO or of L-aromatic amino acid decarboxylase. These treatments have been shown previously to be associated with reduced conversion of glucose to amino acids in brain. Cerebral PLP concentrations were reduced after some of these treatments, notably injection of ethanol, or L-dopa alone or with beta-phenylisopropylhydrazine, an inhibitor of MAO, or of 5-HTP together with N-[beta-(chlorophenoxy)ethyl]cyclopropylamine hydrochloride, Lilly 51641, another MAO inhibitor. However, in other circumstances where inhibition of conversion of glucose to amino acids has been shown (treatment with 5-HTP, or with Lilly 51641 or with [N-(D,L-seryl)-N'-2,3,4-trihydroxybenzyl]hydrazine, an inhibitor of L-aromatic amino acid decarboxylase, together with L-dopa or with 5-HTP), PLP levels in brain were unchanged, or were increased (in hepatectomized rats).

5-Hydroxytryptophan↗
PubMed1979

Measurement of endogenous norepinephrine overflow from canine saphenous veins.

A method for the measurement of norepinephrine (NE) overflow from isolated superfused canine saphenous veins is described. This method involves concentrating NE present in the superfusate, followed by measurement of its concentration by high-performance liquid chromatography with electrochemical detection. The limit of sensitivity of the method (defined as a signal-to-noise ratio of 5) was 25 pg. NE concentration measured by this method correlated well (r = 0.95) with that measured by standard fluorometric methods. Electrical stimulation caused an initial overflow of a mean of 115 X 10(-18) mol NE/mg of vein per pulse; this was associated with an increase in isometric tension. With continued stimulation, less NE overflowed into the superfusate, although tension was not reduced appreciably.

Animals↗
PubMed1979

Nerve growth factor-enhanced reinnervation of surgically denervated canine heart.

Nerve growth factor (NGF) was administered in doses of 25,000 U daily for the first 5 postoperative days to dogs subjected to cardiac denervation. These dogs and untreated cardiac-denervated dogs were killed at 1, 2, 3, and 6 mo postoperatively. Tritiated norepinephrine ([3H]NE) was administered prior to death, after which the hearts were removed and eight segments (right and left atria, right ventricular conus and sinus, left ventricular base and apex and high and low ventricular septum) analyzed to determine myocardial NE content and uptake of [3H]NE. Our data demonstrated enhanced cardiac reinnervation of the left ventricular base in NGF-treated dogs.

Animals↗
PubMed1979

Dipyridamole levels in plasma of man and other species.

Measurements were made of the concentration of dipyridamole in the plasma of man, dogs, pigs, and pigeons at different times after oral administration of the drug. In dogs and in man, there was considerable variation in the plasma levels of the drug in different subjects. Pigs and pigeons always had much lower levels of the drug in plasma than did men and dogs given comparable doses. After intravenous injection of dipyridamole to pigs, a large proportion of the drug appeared to leave the plasma almost immediately; subsequently, the half-life of the drug remaining in the plasma was quite similar to that previously reported in man. The administration of aspirin with dipyridamole sometimes resulted in higher blood levels of the drug in dogs, man, and pigs, but the effects were small. The wide variations in plasma drug levels observed indicate that in future human or experimental trials designed to evaluate the antithrombotic effect of dipyridamole, plasma levels of the drug should be routinely monitored.

Administration, Oral↗
PubMed1979

Analysis for urinary catecholamines by liquid chromatography with amperometric detection: methodology and clinical interpretation of results.

A method is presented for the quantitative analysis of urinary unconjugated norepinephrine, epinephrine, and dopamine as discrete entities. The procedure requires initial purification of the specimen on aluminum oxide and a boric acid-gel. We used "high-performance" reversed-phase paired-ion chromatography, with a flow-through amperometric cell as the detector. The CV was 6% for determination of norepinephrine, 11% for epinephrine, and 6% for dopamine monitored at physiologic concentrations of these compounds in urine. In a population study, urine specimens from 117 normal pediatric and adult subjects, 85 hypertensive patients, and 22 patients with surgically proved pheochromocytoma were analyzed. The specificity of the method for detection of pheochromocytoma was 100%, with a sensitivity of 97%.

Adolescent↗
PubMed1978

A potential artifact in use of a new technique for rapid brain removal.

New techniques are are continuously being developed to obtain animal brain tissue that is as close as possible to its in vivo status. The brain-blowing technique provides a swift freezing of brain tissue (within 1 s) in which postmortem changes have been said to be minimal. Higher concentrations of glucose were present in brain samples removed by this method than have previously been found when the brain was frozen in situ, but at the same time the plasma levels of glucose were higher. It is suggested that, although the procedure did not appear to involve any stress, the hyperglycemia was stress related. Modifications of the procedure are described, by which these changes in blood glucose have been minimized.

Animals↗
PubMed1978

Demethylation in erythrocytes: a reaction involving hemoglobin.

A reaction is described in erythrocytes of rat and of man whereby O-methylated metabolites of the catecholamines are demethylated to the corresponding catechols. The reaction was studied by incubating aliquots of erythrocyte lysates with radiolabeled O-methylated compounds and isolating the catechol product by alumina adsorption chromatography. The demethylating activity was located in the cytosol of the erythrocytes. Evidence was strong that oxyhemoglobin was responsible for the reaction: the demethylase activity was inseparable from oxyhemoglobin in several chromatographic separations. In addition, although commercially available hemoglobins were inactive in the reactions, after their conversion to oxyhemoglobin and purification, they did effect demethylation. Methemoglobin did not demethylate guaiacols and in fact inhibited demethylation by oxyhemoglobin. The reaction was inhibited by the addition of reduced pyridine nucleotides and of the methyl acceptor tetrahydrofolic acid.

Animals↗
PubMed1978

Norepinephrine metabolism in canine saphenous vein: prevalence of glycol metabolites.

To examine the disposition of [3H]norepinephrine ([3H]NE) in adrenergically innervated veins, helical strips of canine saphenous veins were incubated in Krebs-Ringer solution containing D,L[3H]NE (2 X 10(-7) M) for 2 h. [3H]NE and its metabolites were measured in extracts of veins and in superfusate (Krebs-Ringer) collected during basal conditions and during release of [3H]NE evoked by electrical stimulation (1-8 Hz), tyramine (5 X 10(-6) to 5 X 10(-4) M), or high concentrations of potassium (35-100 meq/liter). During basal conditions, the efflux from veins comprised mainly metabolits of [3H]NE, especially 3,4-dihydroxphenylglycol (DOPEG) and 3-methoxy-4-hydroxyphenylglycol (MOPEG); this pattern was unchanged by cocaine treatment, and monoamine oxidase inhibition reduced the formation of DOPEG. During evoked release of NE, the major metabolites in the perfusate were DOPEG, MOPEG, and normetanephrine, and their proportions differed with the stimulus used: O-methylated metabolites in the perfusate always increased more than did the deaminated catechol compounds; DOPEG and MOPEG were released in greater amounts than the corresponding acids; and cocaine treatment caused a higher content of all metabolites except DOPEG. 3-Methoxy-4-hydroxymandelic acid was also formed by the vein but was retained in the tissue.

Animals↗
PubMed1978

Norepinephrine uptake as an indicator of cardiac reinnervation in dogs.

To study the possible role of uptake of [3H]norepinephrine ([3H]NE) as an indicator of sympathetic reinnervation of the surgically denervated canine heart, uptake was determined from multiple areas of hearts at various stages of reinnervation (1--6 mo), and these data were correlated with myocardial catecholamine content and functional response of the heart to electrical stimulation of the sympathetic nerves. Our experiments confirm that NE content correlates poorly with the degree of reinnervation of the previously denervated canine heart. There is, however, a progressive increase of [3H]NE uptake from 1 mo to 6 mo, at which time uptake has returned to approximately 57% of control values in the left atrium. The development of the storage mechanism lags far behind the specific-membrane mechanism for uptake in the reinnervating surgically denervated canine heart.

Animals↗
PubMed1978

Acetylcholine--inhibition of transmitter release from adrenergic nerve terminals mediated by muscarinic receptors.

The evidence is reviewed for the presence of muscarinic receptors on the sympathetic nerves to blood vessels. Activation of these receptors by acetylcholine in doses that are too small to affect the smooth muscle cells directly inhibits the release of norepinephrine evoked by electric impulses or potassium ions. This inhibitory action of acetylcholine is prevented by muscarinic blocking agents and is probably due to hyperpolarization of the adrenergic nerve terminals.

Acetylcholine↗