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Biomedical subjects

G M Tyce

Publications and source records attributed to G M Tyce.

At least 73 records · Page 4Linked to original sources
PubMed1989

Exercise training produces changes in free and conjugated catecholamines.

In dogs the concentrations of conjugated dopamine in plasma have previously been shown to increase after exercise training. This study was done to determine whether conjugated norepinephrine and epinephrine also increase. Fifteen dogs were randomly divided into training (N = 8) or sedentary (N = 7) groups. All dogs were exercised acutely for 5 min at 4 mph with a 12% grade, following a 3-min warm-up, before and after either a 12-wk training or a 12-wk sedentary period. Free and conjugated catecholamines were determined in blood drawn at rest and during acute exercise using high-performance liquid chromatography (HPLC) with electrochemical detection. Before training, free norepinephrine, epinephrine, dopamine, and conjugated norepinephrine increased in plasma during acute exercise. Following the 12-wk training period, there were significant increases in free and conjugated dopamine and in conjugated norepinephrine in plasma taken at rest. There were no such increases in resting catecholamines after a 12-wk sedentary period. After either training or sedentary periods, dogs responded to acute exercise with an increase in free norepinephrine and a decrease in conjugated norepinephrine. Thus, after training both conjugated norepinephrine and dopamine, but not conjugated epinephrine, increased in plasma. The data suggest that sulfation of catecholamines increases as a result of exercise training.

Animals↗
PubMed1989

Catecholamines in CSF, plasma, and tissue after autologous transplantation of adrenal medulla to the brain in patients with Parkinson's disease.

Catecholamine concentrations were measured in tissue samples of caudate and adrenal medulla in eight patients with Parkinson's disease who were taking L-dopa and were undergoing autologous transplantation of adrenal medulla to caudate nucleus. High-performance liquid chromatography with electrochemical detection was used for the measurement of analytes. Dopamine concentrations were quite similar in the caudate and the adrenal medulla; epinephrine and norepinephrine concentrations were some 600 times and 90 times higher, respectively, than that of dopamine in adrenal medulla but were barely detectable in caudate nucleus. Catecholamines and metabolites were also measured, before and after transplantation, in lumbar cerebrospinal fluid (CSF) and plasma 1 hour after the patients' first morning dose of L-dopa. The major fractions of the catecholamines in CSF were sulfoconjugated. The concentrations of sulfoconjugated but not free dopamine were modestly increased in CSF after the transplantation, although plasma concentrations were unchanged. CSF concentrations of free and conjugated norepinephrine and epinephrine, 3-methoxy-4-hydroxyphenylglycol, and homovanillic acid were unchanged after the transplantation. The data suggest that the grafted tissue does not retain its noradrenergic or adrenergic properties after transplantation, and that dopamine formation in the brain may be modestly increased. Plasma catecholamines were unaffected after the removal of one adrenal gland for the transplant.

Adrenal Medulla↗
PubMed1988

Sympathetic stimulating effects of sufentanil in the cat are mediated centrally.

The hemodynamic and adrenal secretory response to sufentanil (25 micrograms/kg i.v.) was evaluated during halothane anesthesia in 3 groups of cats: group I, n = 5, control; group II, n = 4, naloxone pretreatment (3 mg/kg i.v.); and group III, n = 5, acute spinal transection at T3-4. Administration of sufentanil in intact cats (group I), caused a significant increase in mean arterial blood pressure and adrenal vein plasma levels of norepinephrine, epinephrine, dopamine, and Met-enkephalin. These effects were abolished in naloxone-pretreated cats (group II). Following spinal transection (group III), sufentanil evoked a significant increase in blood pressure and heart rate, but no change in adrenal hormone levels. Intraventricular injections of sufentanil suggest that these sympathetic stimulating effects are mediated at central sites in proximity to the lateral and third ventricle.

Adrenal Medulla↗
PubMed1988

Concurrent separation of catecholamines, dihydroxyphenylglycol, vasoactive intestinal peptide, and neuropeptide Y in superfusate and tissue extract.

A method is described for separation and quantification of 3,4-dihydroxyphenylglycol (DO-PEG), norepinephrine (NE), dopamine (DA), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) from single samples of tissue homogenate and from superfusate from in vitro dog blood vessel preparations using cartridges containing 0.4 g of octadecylsilane (Sep-Pak C-18). Samples were passed through the cartridge at pH 7.4. A step-gradient system was used to first selectively desorb the catechols (DOPEG, NE, DA) with a moderately polar eluent; subsequently VIP and NPY were eluted with 2.5 ml of a mixture of 1% trifluoroacetic acid, 80% acetonitrile. Five Sep-Pak catechol eluents were tested. Catechols were quantified by HPLC with electrochemical detection and peptides by radioimmunoassay. An HPLC solvent system is described which is particularly useful for chromatography of the more hydrophilic catechols DOPEG, 3,4-dihydroxymandelic acid, and 3,4-dihydroxyphenylalanine concurrently with catecholamines. For superfusion studies, sample cleanup time was reduced to about 4 min per sample by attachment of the cartridges directly to the bottom of the superfusion chamber. Superfusate was subsequently pulled through the cartridges immediately after they were passed over the tissue. Batches of 12 high-speed tissue supernates were processed through the method in about 30 min. The method was used to analyze DOPEG, NE, DA, VIP, and NPY in various rat and dog tissues. The values obtained were similar to values obtained previously by other methods. Because the catechols and peptides are separated from a single sample, the method has several advantages over those described previously; e.g., it is rapid, simple, and more sensitive.

Animals↗
PubMed1988

Chronic hypoxia alters structure and transmitter dynamics in dog pulmonary artery.

Confinement of dogs to 10% oxygen for 14 days caused erythropoiesis and pulmonary hypertension. Histological sections of the lung tissue showed thickening of the smooth muscle component of muscular arteries and arterioles. Segments of pulmonary artery from dogs exposed to hypoxia were superfused under continuation of hypoxic conditions or after return to oxygenated conditions. Parallel segments of pulmonary artery from normal dogs were also studied. Norepinephrine stores were labeled with [3H]norepinephrine and measurements were made of [3H]norepinephrine and its radiolabeled metabolites (separated by column chromatography) in superfusates using liquid scintillation spectrometry. Chronic hypoxia (1) reduced neuronal uptake of NE from synaptic clefts, (2) reduced the content of DOPEG in superfusate from tissues studied during continuation of hypoxic conditions and in tissues studied after return to oxygenated conditions, (3) increased extraneuronal uptake of NE and (4) increased overflow of NE from synaptic clefts. In similar segments of pulmonary artery removed from the same lung, endogenous free and conjugated norepinephrine and dopamine were measured in pulmonary artery by liquid chromatography with electrochemical detection. The tissue content of free norepinephrine after stimulation was reduced, which was compatible with the reduction in neuronal uptake. Conjugated norepinephrine was a minor metabolite and was increased modestly compared to concentrations reported previously in pulmonary artery from normal dogs.

Animals↗
PubMed1988

Effect of acute and chronic spinal transection on evoked secretion of adrenal medullary catecholamines in the cat.

Eight cats were spinally transected at T3. After an acute (0-5 days) or chronic (15-37 days) period, animals were rendered decerebrate and the effects of visceral (bladder distention) and somatic (sciatic nerve stimulation) stimuli were examined. Epinephrine, norepinephrine and dopamine levels were measured in plasma collected from the left adrenolumbar vein; heart rate and blood pressure were continuously monitored. In chronic animals both visceral and somatic stimuli most frequently evoked prominent increases in blood pressure and the secretion of adrenal medullary catecholamines; the same stimuli caused little change in these parameters in acute animals. These data indicate that a condition similar to the clinical syndrome of autonomic hyperreflexia may be elicited in the chronic spinally transected cat, and that this condition is accompanied by a notable activation of the adrenal medulla.

Acute Disease↗
PubMed1988

Opioids preserve the adrenal medullary response evoked by severe hemorrhage: studies on adrenal catecholamine and met-enkephalin secretion in halothane anesthetized cats.

Possible modulatory effects of mu-, delta-, and kappa-receptor agonists on the concurrent adrenal secretion of catecholamines and met-enkephalin evoked by staged hemorrhage were examined in four groups of cats (n = 5 in each group) anesthetized with halothane (1 MAC). Group I received saline, group II received the mu-agonist sufentanil (25 micrograms/kg i.v., followed by a maintenance infusion), group III received the delta/mu agonist metkephamid (3 mg/kg i.v.), and group IV the kappa agonist U50488H (3.5 mg/kg i.v.). Samples for norepinephrine, epinephrine, dopamine, and met-enkephalin were taken simultaneously from the adrenal vein, femoral vein, and femoral artery at baseline, after drug administration, and after induction of 25% and 50% hemorrhage. In cats receiving saline, 25% hemorrhage resulted in a significant decline in mean arterial blood pressure (MABP) and no change in adrenal secretion. Fifty percent hemorrhage evoked no significant further fall in MABP, but led to prominent increases in adrenal vein hormone levels (norepinephrine, 30-fold; dopamine, 14-fold; and epinephrine, ten-fold) as compared to post-saline values. During the pre-hemorrhage baseline state, administration of sufentanil evoked a significant six- to 20-fold rise in adrenal vein catecholamine and met-enkephalin levels, whereas the administration of metkephamid and U50488H produced no change in adrenal secretion and a decrease in MABP. After 25% and 50% hemorrhage, there was no difference in adrenal vein hormone levels in cats receiving the mu-, delta-, or kappa-agonists compared to those receiving saline. No differences were observed in the different treatment groups with regard to the proportional levels of catecholamines and met-enkephalin in the adrenal vein during the course of the experiment. The authors conclude that opioids are not involved in the regulation of the secretory adrenal medullary response evoked by hemorrhage, and that the systems involved in mediating these cardiovascular reflexes differ pharmacologically from those systems mediating the autonomic response evoked by pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1988

Differences in norepinephrine dynamics in large and small pulmonary arteries of dog.

These studies address the apparent dissociation between the amounts of norepinephrine (NE) released from small and large pulmonary arteries of dogs by a standard electrical stimulus and the contractile tensions that developed in these tissues. Segments of vessels were studied in organ baths or in a superfusion apparatus during electrical stimulation. Endogenous NE was quantitated using liquid chromatography with electrochemical detection. 'Release' of NE was studied under conditions in which uptakes of NE from the synaptic cleft were impaired, and overflow of NE was studied when these uptakes were operative. 'Release' of NE was predictably greater than overflow in all arteries. In the large pulmonary artery, greater contractile tensions were measured when greater amounts of NE were present in superfusate. In the small pulmonary artery, contractile tensions did not directly correlate with the amounts of NE measured in the superfusate. These studies indicate that NE dynamics are different at neuroeffector junctions in large and small pulmonary arteries. Several explanations to account for these differences are discussed.

Animals↗
PubMed1988

Free and conjugated plasma catecholamines, DOPA and 3-O-methyldopa in humans and in various animal species.

The aim of the present study was to determine the extent to which plasma catecholamines are conjugated in different animals compared to man and how widespread is the presence of dihydroxyphenylalanine (DOPA) and 3-methoxy-4-hydroxyphenylalanine (3-OMD) in plasma among the different animal species. Free and conjugated norepinephrine, epinephrine, and dopamine were measured in plasma in humans and in several animal species (dog, rat, Gunn rat, cat, rabbit, guinea pig, African green monkey, young pig, calf, and one American black bear) using HPLC with electrochemical detection. The same technique was used to measure free and conjugated DOPA and 3-OMD in plasma of man, dog, rat, Gunn rat, calf, and American black bear. Human plasma contains the highest concentration of total (free and conjugated) catecholamines (46.1 pmole/ml), while low concentrations (below 15 pmole/ml) were observed in unstressed rats, calves, cats, and young pigs. In man, 95.3% of total plasma catecholamines were conjugated. The extent to which plasma catecholamines were conjugated varied greatly between animal species. The conjugated fraction expressed as percentages of the total catecholamines is lowest in the young pig (4.7%) and highest in the bear (100%). Conjugated dopamine was present in the plasma of all species, varying between 3% of the total catecholamine pool in young pig to 90% in dog. Conjugated norepinephrine was also present in plasma of all species except in unstressed rats with access to food. Conjugated epinephrine was detected only in cat and rat. Free DOPA and 3-OMD were present in plasma of all tested species with especially high levels of 3-OMD being present in dog. Conjugated DOPA and 3-OMD were not consistently found in any species. Our results indicate that man, dog, bear, and African green monkey are particularly good catecholamine conjugators and that young pig, guinea pig, rabbit, and calf are poor conjugators.

Adult↗
PubMed1987

Effects of hemorrhage and naloxone on adrenal release of methionine-enkephalin and catecholamines in halothane anesthetized dogs.

Concurrent levels of methionine-enkephalin and catecholamines in adrenal vein, femoral vein and femoral artery were measured under baseline conditions and during graded hemorrhage in halothane anesthetized dogs and compared to a non-bled control group. Naloxone was administered in both groups at the end of the experiment. Normotensive hypovolemia with a remaining blood volume of 76% led to a moderate decrease in mean arterial blood pressure from baseline and a 15- to 20-fold increase in norepinephrine, epinephrine and dopamine, and a 5-fold increase in enkephalin in the adrenal vein. Subsequent induction of hypotensive hypovolemia with a remaining blood volume of 51% resulted in a profound drop in blood pressure and evoked a further increase in the level of catecholamines (40- to 50-fold from baseline) and enkephalin (8-fold from baseline) in the adrenal vein. In the control group only a 3- to 4-fold increase from baseline in adrenal vein hormone levels was observed over time. Naloxone administration at the end of the experiment, led to a 2- to 6-fold further increase in hormones at the 3 collection sites in both groups of dogs. Joint calculation of the partial correlation coefficients for the influence of preceding blood volume and blood pressure, and concurrent blood volume and blood pressure on hormone secretion in the adrenal vein revealed that these variables explained the variation in hormone levels between 56 and 92% during normotensive hypovolemia and 62-83% during hypotensive hypovolemia. In one dog with bilateral adrenalectomy, hemorrhage was poorly tolerated, and naloxone administration did not lead to increased systemic plasma levels of catecholamines and enkephalin or improved hemodynamics. In the hemorrhage group, molar ratios of norepinephrine/epinephrine in the adrenal vein showed a significant increasing trend during the experiment. Findings in these experiments support the idea of differential monoaminergic and enkephalinergic regulation in adrenal medullary cells.

Adrenal Glands↗
PubMed1987

Intrathecal 6-hydroxydopamine or cervical spinal hemisection reduces norepinephrine content, but not the density of alpha 2-adrenoceptors, in the cat lumbar spinal enlargement.

The effect of the intrathecal administration of the catecholaminergic neurotoxin 6-hydroxydopamine, or of hemisection of the spinal cord at the Cl level, on the density of alpha 2-adrenoceptors and on the norepinephrine, dopamine, and serotonin content in the cat lumbar spinal enlargement was determined 2, 7 or 21 days after performance of each type of lesion. The intrathecal administration of 6-hydroxydopamine produced a time-dependent reduction of norepinephrine content in the cat lumbar spinal enlargement (95% reduction at 21 days) without significantly altering the serotonin content in this same tissue of the same cats. The dopamine content of the dorsal horn was not changed significantly, whereas ventral horn dopamine content was depleted after intrathecal 6-hydroxydopamine. alpha 2-Adrenoceptor binding site density was not significantly different from control either 2 or 21 days after 6-hydroxydopamine, but was increased significantly (50%) over the control density 7 days after 6-hydroxydopamine. Hemisection of the cervical spinal cord produced a bilateral 40-60% reduction of norepinephrine content in both the dorsal and ventral horns of the cat lumbar spinal enlargement 7 and 21 days later. Cervical hemisection did not significantly alter the alpha 2-adrenoceptor binding site density in these same cats either 2, 7, or 21 days after performance of the lesion. It is concluded that alpha 2-adrenoceptors located on the terminals of descending noradrenergic or other spinopetal fibers do not represent a significant fraction of the total population of alpha 2-adrenoceptors present in the dorsal or ventral cat lumbar enlargement.

Adrenergic Fibers↗
PubMed1987

Free and conjugated catecholamines in dog pulmonary artery: presence and pharmacological action.

Free and conjugated forms of norepinephrine (NE) and dopamine (DA) were detected in dog pulmonary artery, and small amounts were released during 2-Hz electrical stimulation. Hydrolysis of the conjugates by acid boiling and by enzymes indicated that they were primarily sulfates, but traces of glucuronide may also have been present. After isolation by column chromatography, free and conjugated amines were quantitated using liquid chromatography with electrochemical detection. Pulmonary artery tissue contained (in ng) 1,240 +/- 100 free NE, 15 +/- 5 conjugated NE, 47 +/- 6 free DA, and 2 +/- 0.3 conjugated DA/g tissue (means +/- SE). When strips of pulmonary artery were immersed in [3H]NE small amounts of [3H]NE sulfate were synthesized. The release of conjugated NE was not calcium dependent but release was attenuated somewhat by tetrodotoxin. Removal of endothelium did not change tissue content of conjugated or of free NE nor the amounts measured in superfusate. Small amounts of free DA were also detected in tissues and in superfusate during stimulation, but only when calcium was present in the superfusion fluid. Norepinephrine sulfate was not a potent agonist at either pre- or postsynaptic alpha-receptors; the agonist activity seen with high concentrations of norepinephrine sulfate seems likely to have been due at least in part to trace contamination by free NE.

Adrenergic alpha-Agonists↗
PubMed1987

Human liver and conjugation of catecholamines.

To investigate the role of the liver in conjugation of catecholamines we measured the concentrations of free and conjugated norepinephrine, epinephrine, and dopamine in plasma of patients with severe liver disease who were undergoing liver transplantation. Comparisons were made with catecholamine levels in plasma of euhepatic patients who were undergoing abdominal aortic aneurysmectomy. We were also able to determine the importance of the liver in conjugation of exogenous dopamine because this compound was given to both groups of patients. The concentrations of conjugated amines were within the normal range in the patients undergoing liver transplantation, and administered dopamine was conjugated to a similar extent in the two groups of patients. The data suggest that the liver is not indispensable for the conjugation of circulating catecholamines.

Adult↗
PubMed1986

Conjugates of biogenic amines in ventriculocisternal perfusates of conscious African green monkeys.

To determine the importance of conjugation relative to alternate metabolic pathways for the inactivation of catecholamines and serotonin, free and conjugated norepinephrine, dopamine and serotonin, together with the acid metabolites homovanillic acid and 5-hydroxyindoleacetic acid, were measured in ventriculocisternal perfusions in awake African green monkeys. Measurements were made of endogenous transmitters and their metabolites using high performance liquid chromatography with electrochemical detection. Efflux of amines and metabolites was measured both under conditions of spontaneous overflow and during release evoked by 40 mM K+ or by 5 X 10(-5) M amphetamine. Conjugated amines were of greater importance under basal conditions than during evoked release. Although more conjugated amines were produced in African green monkey than has been previously detected in other species, conjugation was still minor relative to O-methylation and oxidative deamination. When nomifensine (5 X 10(-5) M), a blocker of neuronal uptake of dopamine, was added to perfusion fluids, the efflux of free dopamine was increased. Efflux of conjugated dopamine was not decreased in the presence of nomifensine, suggesting that conjugation did not occur subsequent to reuptake of transmitter into dopaminergic neurons. Evidence is also presented that different enzymes are responsible for the conjugation of catecholamines and serotonin.

Animals↗
PubMed1986

Increased norepinephrine release from dog pulmonary artery caused by nitrous oxide.

The effects of nitrous oxide on the release and metabolism of norepinephrine (NE) at neuroeffector junctions in dog pulmonary artery were examined. Helical strips of artery were incubated in Krebs-Ringer solution containing L-(3H)NE and mounted for superfusion. The arterial strips were studied in the presence of 95% oxygen-5% carbon dioxide, 70% nitrogen-30% oxygen, or 70% nitrous oxide-30% oxygen. During the 60 min of each experiment, five samples of superfusion fluid were collected for analysis and the effluxes of (3H)NE and its radiolabeled metabolites were measured before and during electrical stimulation and during recovery from stimulation. (3H)Norepinephrine was separated from its metabolites in the superfusate and in extracts of artery by column chromatography and quantitated by liquid scintillation spectrometry. Nitrous oxide significantly increased the fractional loss of total radioactivity and the amount of NE in the superfusate both during resting conditions and during stimulation. Nitrous oxide had no effect on the proportions of radioactivity among metabolites of NE in the superfusate or on the profile of NE metabolites remaining in the tissue after experimentation. These findings are consistent with increased NE release as a direct effect of nitrous oxide on nerve endings.

Animals↗
PubMed1986

Amine sulfate formation in the central nervous system.

The sulfates of norepinephrine, dopamine (DA), and serotonin (5-hydroxytryptamine [5HT]) are present in the cerebrospinal fluid (CSF) of laboratory animals and humans. The amounts of sulfated amines in human CSF always greatly exceed the amounts of the free amines. The enzyme responsible for sulfation, phenol sulfotransferase (PST) (EC 2.8.2.1), has been detected in the brain tissue of several species, including humans. PST in the human brain has a high affinity for the amines but it is a low-capacity enzyme. Accordingly, sulfation appears to be of greater significance in the economy of the amines under quiescent conditions than during conditions of increased release of transmitter. Recent evidence suggests that a fraction of the conjugated amines in CSF enters from plasma because in the African green monkey, DA sulfate and 5HT sulfate cross the blood-CSF barrier after i.v. injection. In addition, in humans there are no increases in the concentration of amine sulfates from lumbar to ventricular CSF that would also be compatible with a partly peripheral origin for the amine sulfates. However, it appears that at least a portion of the amine sulfates in CSF originate in the central nervous system because the ratios of [CSF amine sulfates]/[plasma sulfates] are never as high after i.v. injection as under basal conditions.

Animals↗
PubMed1986

Norepinephrine uptake in canine saphenous veins in the presence and absence of halothane.

Studies were done to examine neuronal and extraneuronal uptakes of norepinephrine in canine saphenous veins and to ascertain whether these uptakes were altered by halothane. Minced vein was incubated for 1 min in Krebs-Ringer solution containing L-[ring-2,5,6-3H]-norepinephrine (1, 2.5, 6, or 12 microM). After incubation, radioactivity in tissue was measured by liquid scintillation counting. Neuronal uptake at each norepinephrine concentration was determined by the difference in norepinephrine uptake between tissues in which both neuronal and extraneuronal uptakes were operative and in tissues in which only extraneuronal uptake was operative. In time studies with 1 microM norepinephrine, neuronal uptake was still dominant at 10 min; with 12 microM norepinephrine, extraneuronal uptake predominated at all incubation periods tested. In other studies, tissues were incubated in the absence or presence of halothane (2.5%). The Km values for neuronal uptake in control and halothane-treated tissues were 2.49 and 2.32 microM, respectively. Corresponding Vmax values were 0.049 and 0.060 nMol X min-1 X 100 mg-1, respectively. No significant effect of halothane on neuronal or extraneuronal uptake could be detected.

Animals↗