Biomedical subjects

G M Tyce

Publications and source records attributed to G M Tyce.

At least 37 records · Page 2Linked to original sources

PubMed1995

Concentrations of 3,4-dihydroxyphenylalanine and catecholamines and metabolites in brain in an anhepatic model of hepatic encephalopathy.

Alterations in the catecholaminergic neurotransmitter systems have been shown to occur in hepatic failure and may contribute to development of hepatic encephalopathy. In the present study we used the rat after complete hepatectomy as a model for study of changes that occur in brain in acute liver failure. We attempted to identify processes in the synthesis, storage, and metabolism of catecholamine neurotransmitters that might be changed during liver failure by measuring levels of, together with those of norepinephrine and dopamine, the precursor (3,4-dihydroxyphenylalanine) and the neuronal metabolites of dopamine and norepinephrine (3,4-dihydroxyphenylacetic acid and 3,4-dihydroxyphenylglycol, respectively) in different regions of brains of control rats and of rats after hepatectomy. We found that in most brain regions of hepatectomized rats there were increases in the concentration of 3,4-dihydroxyphenylalanine or of dopamine but decreases in the concentrations of norepinephrine or of 3,4-dihydroxyphenylglycol. The particulate/supernatant ratios of catecholamines are indices of retention of neurotransmitters in storage sites. These ratios were not different in brain regions between control rats and hepatectomized rats, suggesting that vesicular retention of catecholamines in brain was not impaired after hepatectomy. The data suggest that inhibition of dopamine-beta-hydroxylase might be a characteristic of hepatic failure.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Catecholamine release and excretion in rats with immunologically induced preganglionic sympathectomy.

Plasma and urinary catecholamines were quantified to assess global sympathoadrenal function in rats with preganglionic lesions caused by antibodies to acetylcholinesterase (AChE). Rats were given intravenous injections of normal mouse IgG or murine monoclonal anti-acetylcholinesterase IgG (1.5 mg). Five or 16 days afterward, basal blood samples were taken through indwelling arterial cannulate. A few hours later, the rats were immobilized for 10 min in padded restrainers, and another blood sample was drawn. HPLC determinations showed low basal levels of norepinephrine and epinephrine (< 0.2 ng/ml in all rat plasma samples). In control rats, immobilization stress increased levels of plasma catecholamines up to 35-fold. In rats tested 5 days after injection of antibody, the norepinephrine response was much smaller (15% of control), and the epinephrine response was nearly abolished (5% of control). There was some recovery at 16 days after antibody treatment, but stress-induced catecholamine release was still markedly impaired. Reduced stress-induced release was not accompanied by major changes in tissue epinephrine or norepinephrine (heart, spleen, adrenal glands, and brain), although adrenal dopamine content dropped by 60%. Urinary excretion was studied in parallel experiments to gain insight into the effects of AChE antibodies on basal sympathoadrenal activity. Epinephrine, norepinephrine, dopamine, and selected metabolites were quantified in 24-h urine samples collected at frequent intervals for 30 days after antibody injection. No statistically significant changes were detected in the urinary output of dopamine, 3-methoxytyramine, normetanephrine, or 3-methoxy-4-hydroxyphenylglycol. On the other hand, epinephrine and norepinephrine output increased sharply at the time of antibody injection and then fell significantly below control levels. Norepinephrine output returned to normal after 2 weeks, but epinephrine output remained depressed. These results are consistent with previous evidence of widespread and persistent antibody-mediated damage to the preganglionic sympathetic system.

Acetylcholinesterase↗

PubMed1994

Effect of increased dietary phosphate intake on dopamine excretion in the presence and absence of the renal nerves.

Studies were performed to determine the relative contributions of the renal nerves and tubule synthesis to dopamine excretion during increased dietary phosphate intake. Rats underwent bilateral renal denervation (n = 5) or sham surgery (n = 5) 1 week prior to the initiation of the balance studies. All rats were placed in metabolic cages and fed 12 g/day of a low phosphate diet (LPD, 0.07%, Pi) for 4 days, then high phosphate diet (HPD, 1.8% Pi) for 4 days. Sodium, potassium, and chloride contents were made similar in LPD and HPD by adding sodium chloride and potassium carbonate to the food. Urine samples were collected every 24 h for determination of free dopamine and electrolyte excretions. The mean urinary phosphate excretion for 4 days of LPD was 0.17 +/- 0.11 mmol/day in the group with bilateral renal denervation and 0.18 +/- 0.11 mmol/day in the group with innervated kidneys. Likewise, dopamine excretion was similar in both groups in the absence (2.5 +/- 0.2 microgram/day) and in the presence (2.3 +/- 0.1 microgram/day) of the renal nerves in rats fed LPD. Increasing dietary phosphate intake from 0.07 to 1.8% significantly increased urinary phosphate and dopamine excretions. The mean urinary phosphate excretion for 4 days was similar in the denervated (4.4 +/- 0.9 mmol/day) and innervated (4.1 +/- 0.5 mmol/day) groups. The mean urinary dopamine excretion for the 4 days of HPD significantly increased to 4.5 +/- 0.5 microgram/day in the group with chronic bilateral renal denervation and 3.7 +/- 0.2 microgram/day in the group with innervated kidneys. Plasma 3,4-dihydroxyphenylalanine (DOPA) and dopamine levels were not changed by increased dietary phosphate intake. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Inhibition of aromatic L-amino acid decarboxylase under physiological conditions: optimization of 3-hydroxybenzylhydrazine concentration to prevent concurrent inhibition of monoamine oxidase.

The activity of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) is commonly studied indirectly by quantifying the formation of the product, 3,4-dihydroxyphenylalanine (DOPA), after inhibition of aromatic L-amino acid decarboxylase (AAAD; EC 4.1.1.28), the enzyme which metabolizes DOPA. This study was done to determine if the concentration of the hydrazine derivative 3-hydroxybenzylhydrazine (NSD-1015), a drug frequently used in vitro to inhibit AAAD, could be adjusted such that it would inhibit that enzyme, but would not simultaneously inhibit a second, potentially important enzyme, monoamine oxidase (MAO; EC 1.4.3.4). MAO catalyzes the formation of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG) from dopamine (DA) and norepinephrine (NE), respectively. Five concentrations of NSD-1015 in superfusate (0.01 to 20 microM) were tested in strips of canine portal vein superfused and stimulated in vitro. DOPA, DA, NE, and DOPEG in superfusate and in the veins after superfusion were quantified by HPLC with electrochemical detection. The efficacy of NSD-1015 in inhibiting AAAD and MAO was determined by examining the levels of DOPA and DOPEG, respectively. NSD-1015, only when applied at 0.1 microM, resulted in the marked augmentation of total DOPA levels, but did not affect levels of DOPEG, which suggests that this concentration of the drug inhibits AAAD, but does not inhibit MAO. Therefore, it is concluded that, of the concentrations of NSD-1015 tested, 0.1 microM is the optimum concentration to use in this preparation for studies designed to examine TH activity by measuring DOPA after the inhibition of AAAD.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Catecholamines and phosphate excretion by the remnant kidney.

The remnant kidney (RK) exhibits an enhanced fractional excretion of phosphate (FEPi) even in the absence of parathyroid hormone (PTH). Thus, factors other than PTH contribute to this adaptive phosphaturia. Dopamine (DA) infusion is phosphaturic, whereas stimulation of adrenoreceptors is antiphosphaturic. Therefore, the hypothesis that alterations in catecholamines by the RK may be associated with the phosphaturia exhibited by this model was tested. Male Sprague-Dawley rats were subjected to right nephrectomy and surgical ablation of the left renal poles. Four weeks later rats with a RK (N = 10) and control rats with intact kidneys (N = 9) were anesthetized and thyroparathyroidectomized (TPTX). Two hours after TPTX, urine samples were collected for measurements of urinary free DA excretion. Subsequently, 3% inulin in saline was infused for one hour and a 30 minute clearance was taken. The kidneys were then removed and frozen for determination of tissue norepinephrine (NE) and DA concentrations. Glomerular filtration rate was significantly lower in rats with a RK than in controls (0.57 +/- 0.07 vs. 0.83 +/- 0.08 ml/min/g kidney wt), whereas fractional excretion of phosphate (FEPi) was significantly higher (29.4 +/- 4.7 vs. 8.3 +/- 3.4%). Tissue NE concentration was significantly lower in the RK than in the control intact kidney (85.10 +/- 4.95 vs. 129.60 +/- 7.20 ng/g), whereas urinary DA excretion per nephron was significantly higher in the RK (0.12 +/- 0.02 vs. 0.04 +/- 0.006 pg/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Altered release and metabolism of norepinephrine in superfused canine saphenous veins in the presence of halothane and hypoxia.

BACKGROUND: Hypoxia and halothane are both known to have different effects on the release and disposition of norepinephrine at sympathetic nerve terminals during neurotransmission. In adverse clinical situations, both conditions may be present, but the effects of halothane and hypoxia together are not known. Therefore, studies were made of the effects of low partial pressures of oxygen and of halothane on the release, action, and metabolism of norepinephrine at sympathetic nerve endings in isolated segments of a blood vessel in which halothane is known to affect norepinephrine release and action profoundly. METHODS: Saphenous veins were removed from dogs, suspended for superfusion with Krebs-Ringer solution, and stimulated electrically. The veins were exposed to either 0%, 0.75%, or 1.5% halothane in the presence of 95% O2, 5% CO2, or 5% O2, 5% CO2, and 90% N2. Superfusates were collected under basal conditions, during and after electrical field stimulation, and poststimulation. Norepinephrine and its intraneuronal metabolite, 3,4-dihydroxyphenylglycol, were measured in superfusates and in the tissues after superfusion using high-performance liquid chromatography with electrochemical detection. RESULTS: Halothane decreased 1) evoked release of norepinephrine, 2) contractile response of the smooth muscle to nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. However, hypoxia 1) increased evoked release of norepinephrine but decreased 2) contractile response during nerve stimulation, 3) formation of 3,4-dihydroxyphenylglycol, and 4) tissue content of norepinephrine. When halothane and hypoxia were present together, their effects on 3,4-dihydroxyphenylglycol formation, tissue content of norepinephrine, and the contractile responses appeared to be additive, but norepinephrine release was decreased compared with control concentrations. CONCLUSIONS: Although halothane and hypoxia had similar and additive effects on the intraneuronal metabolism of norepinephrine and on the postjunctional responses of smooth muscle to nerve stimulation, they had opposite effects on norepinephrine release from sympathetic nerve endings. The halothane-induced decrease in norepinephrine release overrode the increased release of norepinephrine caused by hypoxia.

Animals↗

PubMed1993

Free and conjugated catecholamines and serotonin in canine thoracic duct lymph: effects of feeding.

The source and fate of sulfoconjugated catecholamines present in plasma are not known. Sulfated norepinephrine has been shown to overflow together with free norepinephrine from a typical peripheral neuroeffector junction. Some released free norepinephrine is removed via the lymphatic system, but it is not known whether sulfated catecholamines are removed similarly. Serotonin, another biogenic amine, is released from the enterochromaffin cells into portal blood. The aims of the present study were to determine whether conjugated catecholamines and serotonin could be detected in thoracic duct lymph of dogs and to compare concentrations in lymph with those in samples of portal blood collected before and after the dogs were fed. A method is described for the extraction and purification of free and conjugated catecholamines and serotonin from lymph. In lymph and in plasma, there were similar concentrations of free (0.2-0.4 ng/ml) and conjugated (0.1-0.2 ng/ml) norepinephrine and of conjugated dopamine (0.2-1.0 ng/ml). The concentrations of free serotonin were much lower in lymph (0.1-0.2 ng/ml) than in portal blood (100-200 ng/ml). Small amounts of conjugated serotonin (0.1-0.4 ng/ml) were detected in lymph but were not detected in plasma. Feeding caused increases in concentration of conjugated dopamine in lymph and in plasma and small increases in the output of free norepinephrine and free and conjugated serotonin in lymph.

Amines↗

PubMed1993

Autocrine/paracrine regulation of renal Na(+)-phosphate cotransport by dopamine.

We tested the hypothesis that dopamine (DA) acts as an autocrine/paracrine regulator of Na(+)-Pi symport in proximal tubules, using opossum kidney (OK) cells as an in vivo model. Both DA and parathyroid hormone (PTH) increased adenosine 3',5'-cyclic monophosphate (cAMP) and inhibited Na(+)-gradient-dependent uptake of 32P but not that of L-[3H]-alanine. Incubation of OK cells with L-dopa, a DA precursor, resulted in accumulation of DA (7.4 nM), a ninefold increase of cAMP in the medium, and an inhibition (-10%) of Na(+)-Pi uptake. Carbidopa, an inhibitor of aromatic-L-amino acid decarboxylase, prevented the formation of DA from L-dopa, the increase in cAMP, and the inhibition of Na(+)-Pi cotransport. Pi-replete OK cells produced more DA (+15%) from L-dopa than Pi-deprived cells; however, the endogenous DA inhibited Na(+)-Pi cotransport both in Pi-deprived and in Pi-replete cells. Thus OK cells can synthesize DA from L-dopa in a quantity sufficient to elicit both the maximum DA-stimulated cAMP accumulation and inhibition of Na(+)-Pi cotransport in the same cell population. Our data, obtained on an in vitro system, support the hypothesis proposing that DA generated in proximal tubular cells can modulate, via cAMP, the Na(+)-Pi symport in the same or adjacent cells. If present in the kidney, this pathway might represent an autocrine/paracrine system that can contribute to regulation of renal Pi homeostasis.

Alanine↗

PubMed1993

Excretion of catecholamines and metabolites in response to increased dietary phosphate intake.

The urinary excretion of free dopamine, norepinephrine, and epinephrine could reflect the contribution of the neural release and filtration of these catecholamines as well as the intrarenal tubular synthesis and metabolism of dopamine. Because these catecholamines are rapidly metabolized, the excretion of the free amines represents only a fraction of the total release and synthesis by the kidney. The present study determined the effect of increasing dietary phosphate intake on the excretion of free dopamine, norepinephrine, and epinephrine and their primary stable metabolites. Seven male rats were placed in metabolic balance cages and fed 12 gm/day of normal phosphate diet (NPD) (0.7% inorganic phosphorus [Pi]) for 4 days and then fed a high phosphate diet (HPD) (1.8% Pi) for 4 days. Twenty-four-hour urine samples were collected for determination of free catecholamines, their major stable metabolites, and electrolyte excretions. The urinary excretion data for the seven rats was combined for all 4 days of each dietary regimen. Increasing phosphate intake from 0.7% to 1.8% significantly increased free dopamine excretion by 23%, from 5.6 +/- 0.2 to 6.8 +/- 0.1 micrograms/day (n = 7, p < 0.05). This increase in free dopamine excretion was associated with similar increases in urinary excretion of dopamine glucuronide, 21.6 +/- 1.3 to 27.9 +/- 1.8 micrograms/day (32%) and the dopamine metabolite DOPAC, 9.4 +/- 0.5 to 12.1 +/- 0.6 micrograms/day (30%) and total dopamine excretion from 32.9 +/- 1.7 to 41.0 +/- 1.9 micrograms/day (27%). Plasma DOPA levels were unchanged by increased dietary phosphate intake; however, plasma norepinephrine levels decreased significantly. Excretion of free or sulfated norepinephrine was not changed by increased phosphate intake. However, excretion of MHPG, a metabolite of norepinephrine and epinephrine, decreased significantly, from 33.7 +/- 2.1 to 23.9 +/- 0.8 micrograms/day, n = 7, p < 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Adrenal medullary secretion with splanchnic stimulation in spinal cats.

This project was undertaken to determine whether previously observed adrenal medullary hyperactivity that developed following high spinal cord transection in the cat could be explained by increased sensitivity of the synapse between the splanchnic nerve and chromaffin cell. The splanchnic nerve was stimulated in acute (2-3 h; n = 7) or chronic (61-64 days; n = 7), spinally transected (T3) cats that were decerebrate and unanesthetized. Mean arterial blood pressure and adrenolumbar venous blood flow were significantly greater in the chronic animals. Stimulation (30 V; 1 ms pulses) was applied at 3 Hz and 30 Hz to deliver the same number of pulses within 3 min. Adrenal medullary secretion (ng/min) of epinephrine (EPI), norepinephrine (NE), dopamine, neuropeptide Y (NPY), [Met]enkephalin (ENK), and encrypted [Met]enkephalin was determined at baseline and in relation to both patterns of stimulation. With near threshold (3 Hz) stimulation, the following differences were observed between groups: (1) secretion of EPI, NPY, and ENK was significantly greater in the chronic than in the acute animals; and (2) preferential secretion of NE was elicited in the acute animals. These observations suggest that there may be some facilitation of the splanchnic nerve--chromaffin cell synapse that occurs over time following high thoracic spinal cord transection. However, it is likely that central, spinal mechanisms also contribute to adrenal medullary hyperactivity.

Adrenal Medulla↗

PubMed1992

Dihydroxyphenylalanine and dopamine are released from portal vein together with noradrenaline and dihydroxyphenylglycol during nerve stimulation.

The overflows of 3,4-dihydroxyphenylalanine, dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol in canine portal vein superfused in vitro were studied before, during, and after depolarization of sympathetic nerve endings. The four compounds were separated from superfusate and from tissue on Sep-Pak C-18 cartridges and quantified by HPLC with electrochemical detection. Physiological and biochemical methods were used to show that the compound released was most probably 3,4-dihydroxyphenylalanine; the identity of the other endogenous compounds has been established previously. Release of 3,4-dihydroxyphenylalanine was calcium and frequency dependent, inhibited by a-m-L-p-tyrosine (an inhibitor of tyrosine hydroxylase) and augmented by 3-hydroxybenzylhydrazine (an inhibitor of aromatic amino acid decarboxylase). The overflows of dopamine, noradrenaline, and 3,4-dihydroxyphenylglycol from the vein were calcium and frequency dependent. It was estimated that under control conditions, approximately 80% of the total 3,4-dihydroxyphenylalanine that was synthesized was directed to catecholamine biosynthesis, approximately 8% overflowed from the vein, and approximately 14% remained unchanged within the tissue. It is concluded that 3,4-dihydroxyphenylalanine and dopamine are released together with noradrenaline and 3,4-dihydroxyphenylglycol from portal vein upon nerve depolarization.

Animals↗

PubMed1992

Dopamine enhances the phosphaturic response to parathyroid hormone in phosphate-deprived rats.

Phosphate deprivation results in a resistance to the phosphaturic effect of parathyroid hormone. Dopamine is phosphaturic and is synthesized by kidney proximal tubule, the nephron subsegment where parathyroid hormone inhibits phosphate transport. Thus, to test the hypothesis that phosphate deprivation is associated with low intrarenal dopamine synthesis and that dopamine infusion will overcome the resistance to the phosphaturic response to parathyroid hormone, the following study was performed. The effect of dietary phosphate intake on intrarenal dopamine synthesis, as reflected by urinary dopamine excretion, was determined. Rats were placed in metabolic cages (N = 5) and were fed a low-phosphate diet (0.07% Pi) for 4 days and then a high-phosphate diet (1.8% Pi) for 4 days. Twenty-four-hour urinary dopamine excretion was significantly lower in rats fed a low-phosphate diet (2.53 +/- 0.06 versus 4.10 +/- 0.30 micrograms/day). Further, the effect of dopamine infusion on the blunted phosphaturic response to parathyroid hormone was studied in rats fed a low-phosphate diet for 1, 2, and 3 days. Control clearances were taken 2 h after thyroparathyroidectomy; then, parathyroid hormone (33 U/kg plus 1 U/kg/min), dopamine (25 micrograms/kg/min), or parathyroid hormone plus dopamine were infused for 60 min. Changes in the fractional excretion of phosphate were significantly greater in rats fed a low-phosphate diet infused with parathyroid hormone plus dopamine than in rats fed a low-phosphate diet infused with parathyroid hormone alone (delta 27.9 +/- 5.8 versus 11.2 +/- 2.6% for day 1; 28.4 +/- 1.4 versus 7.1 +/- 3.6% for day 2; and 10.7 +/- 2.8 versus -0.2 +/- 0.2% for day 3; N = 5 for all groups).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Exercise-induced increases in atrial natriuretic factor are attenuated by endurance training.

Short-term exercise has been associated with increased plasma levels of atrial natriuretic factor, a potent dilating and natriuretic hormone. In this study, the effect of exercise training on atrial natriuretic factor release during short-term exercise was investigated in men without a history of cardiovascular or other major disease. A well trained group of 10 men who exercised an average of 6,618 kcal/week was compared with a minimally trained group of 9 men who exercised 1,479 kcal/week. Maximal oxygen uptake was 55.2 ml/kg per min in the well trained group and 42.5 ml/kg per min in the minimally trained group (p less than 0.05). Plasma for atrial natriuretic factor, norepinephrine and epinephrine was obtained at rest, at 4 min of exercise and at maximal exercise. Atrial natriuretic factor was lower at rest in the minimally trained than in the well trained men (23 vs. 35.9 pg/ml, p less than 0.05). At maximal exercise, atrial natriuretic factor increased 2.6 times the value at rest in minimally trained men (59.8 pg/ml, p less than 0.05 vs. rest), but did not change in well trained men (34 pg/ml). In minimally trained men at rest, at 4 min of exercise and at maximal exercise, plasma levels of atrial natriuretic factor correlated with heart rate, cardiac output, mean arterial pressure and plasma levels of norepinephrine and epinephrine; these correlations were not found in the well trained group. Thus, short-term exercise results in a significant increase in atrial natriuretic factor in minimally trained but not in well trained men.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Reduced D2 dopamine and muscarinic cholinergic receptor densities in caudate specimens from fluctuating parkinsonian patients.

Binding of spiperone and 3-quinuclidinyl benzilate (QNB), both labeled with hydrogen 3 (3H), were measured in caudate tissue obtained from 8 living parkinsonian patients at the time of cerebral transplantation. This was clinically homogeneous group of patients. All remained predominantly responsive to levodopa, although with marked disability secondary to clinical fluctuations (short-duration responses) and medication-induced dyskinesias; all were receiving substantial doses of levodopa and 6 of the 8 patients were additionally receiving bromocriptine or pergolide. Binding densities of dopamine D2 receptors, as measured by [3H]spiperone binding, were reduced in this group of patients, compared to caudate specimens from autopsy control subjects. This findings may reflect medication-induced receptor downregulation. Parallel changes occurred with muscarinic cholinergic receptors; [3H]QNB binding was significantly reduced, compared to autopsy control values. This reduction of muscarinic receptors might be due to loss of nigrostriatal terminals that are known to contain muscarinic receptors. Alternatively, muscarinic receptors may have been downregulated by increased corticostriatal glutamatergic input to cholinergic cells, inferred to be present based on the prominent levodopa-induced dyskinesias. Finally, receptor deficits could have been a reflection of more widespread degenerative cerebral disease, although levodopa-refractory symptoms were generally not pronounced in these patients.

Adult↗

PubMed1991

Decreased levels of [Met]enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide in parkinsonian adrenal medulla.

Adrenal medullary tissue was collected from parkinsonian patients at autopsy and at the time of autologous transplantation of the adrenal medulla to the caudate nucleus, and from nonparkinsonian patients at autopsy and during nephrectomy. Levels of the following neuropeptides were measured by radioimmunoassay in samples of the medullary tissue: neuropeptide Y (NPY), substance P (SP), [Met]enkephalin ([Met]ENK), vasoactive intestinal peptide (VIP), peptide YY, and bombesin-like immunoreactivity. Regression analysis was used to establish a relationship between patient age, time to organ harvest, and peptide levels in nonparkinsonian tissue. Levels of [Met]ENK, VIP, NPY, and SP were significantly lower in parkinsonian adrenal medullae than that predicted from the control group. These results suggest that the adrenal medulla of a parkinsonian patient is severely compromised, either by the disease process itself or by the antiparkinsonian medications used to treat the symptoms of the disease.

Adrenal Medulla↗

PubMed1991

Neuropeptide Y and 3,4-dihydroxyphenylglycol effluxes from artery are oxygen sensitive.

Neuropeptide Y-like immunoreactivity (NPY-LI), norepinephrine (NE), and 3,4-dihydroxyphenylglycol (DOPEG), the intraneuronal metabolite of NE, were measured in superfusate before, during, and after electrical stimulation (ES) of nerves and in the tissue extract of dog pulmonary artery after in vitro superfusion. Vessels were stimulated at 12, 6, or 1 Hz. NE and DOPEG were quantified by high-performance liquid chromatography with electrochemical detection, NPY-LI by radioimmunoassay. The Krebs-Ringer superfusate was maintained at a partial pressure of oxygen of either 472, 100, 50, or 20 mmHg. Mean DOPEG efflux was 0.17, 0.15, 0.13, and 0.07 pmol/min during basal conditions and 0.73, 0.39, 0.30, and 0.15 pmol/min, respectively, during 12-Hz continuous stimulation using these four oxygen pressures. Stimulation-evoked efflux of NPY-LI was 1.5, 1.1, 0.3, and 0.2 fmol/min during 12-Hz stimulation. These studies provide evidence that the production and subsequent efflux of DOPEG into superfusate under resting conditions, during ES, and following ES are oxygen sensitive. Additionally, the efflux of NPY-LI from dog pulmonary artery resulting from high frequencies of ES is oxygen sensitive.

Animals↗

PubMed1991

Nicotinic- and muscarinic-evoked release of canine adrenal catecholamines and peptides.

The tissue content and overflow of norepinephrine (NE), epinephrine (Epi), dopamine (DA), Met-enkephalin (Met-Enk), and neuropeptide Y (NPY) from isolated, retrogradely perfused dog adrenal glands were studied. Under resting conditions, approximately 25% of the overflow of autocoids from the glands was Ca2+ dependent; the cholinergic antagonists hexamethonium and atropine had no effects on basal efflux. Stimulation with the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP; 3 or 50 microM) or with the muscarinic agonist pilocarpine (50 microM or 1 mM) evoked releases of autocoids. These releases were blocked or dramatically reduced by appropriate antagonists or by the removal of Ca2+ from the perfusate. Expressed as percentages of tissue stores, the rank order of overflow of autocoids was E approximately DA much greater than NE during resting conditions, DA much greater than E approximately NE during stimulation with 50 microM DMPP, and DA greater than Epi greater than NE during stimulation with 1 mM pilocarpine. These data are consistent with different mechanisms of release for the catecholamines, perhaps from different cell populations. The data support corelease of peptides and catecholamines, although clear pairing of autocoids could not be confirmed.

Adrenal Glands↗

PubMed1991

Catecholamine metabolic pathways and exercise training. Plasma and urine catecholamines, metabolic enzymes, and chromogranin-A.

BACKGROUND: Because acute exercise increases systemic catecholamines, we sought to determine whether exercise training would alter daily or exercise-related catecholamine release and inactivation. METHODS AND RESULTS: In 24-hour urine collections, catecholamines and metabolites provided indexes of overall oxidative deamination, sulfation, and O-methylation. Plasma catecholamines, the sulfoconjugates of each, and chromogranin-A were determined at rest and during exercise in 10 well-trained male subjects and nine minimally trained male subjects (maximal oxygen uptake 55.2 and 42.5 ml/kg/min, respectively), and levels of activities of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), and thermolabile phenolsulfotransferase (TL-PST) were also determined. Plasma-free catecholamines showed minimal differences between the two groups at submaximal exercise (4 minutes) but large differences at maximal exercise, reflecting the different exercise levels attained. Inactivation of plasma catecholamines by sulfation across rest and exercise tended to be greater in the well-trained group, with small increases in both plasma sulfoconjugated dopamine and sulfoconjugated norepinephrine. In the well-trained group, urinary metabolites demonstrated trends toward increased dopamine release (p less than 0.07) and small increases in the daily release of epinephrine and its sulfoconjugated metabolites. Indexes of deamination, sulfoconjugation, and O-methylation, with the exception of a reduced deamination of dopamine and the activities of COMT, MAO-B, and TL-PST were not different in the two groups. CONCLUSIONS: Despite considerable differences in the exercise activities per week between well-trained and minimally trained individuals, there were minimal differences in the release and metabolism of catecholamines at rest or during exercise.

Adult↗