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G M Tyce

Publications and source records attributed to G M Tyce.

At least 19 recordsLinked to original sources
PubMed2001

Nitric oxide modulates evoked catecholamine release from canine adrenal medulla.

Nitric oxide has various actions, acting in a neurotransmitter-like role and also as a paracrine messenger between vascular endothelial and smooth muscle cells. This study was done to determine whether endogenous nitric oxide has a role in modulating evoked catecholamine release from the canine adrenal medulla. Isolated adrenal glands were perfused with Krebs-Ringer solution as a control, or with Krebs-Ringer solution containing either N(G)-monomethyl-L-arginine (L-NMMA; 3x10(-4) M) to non-selectively inhibit nitric oxide synthase or 7-nitroindazole (10(-4) M), a relatively selective inhibitor of neuronal nitric oxide synthase. Catecholamine release was evoked using the nicotinic cholinergic agonist 1,1-dimethyl-4-phenylpiperazinium iodine. From the collected perfusate epinephrine, norepinephrine, and dopamine were measured by high performance liquid chromatography. Previous studies have shown that in the presence of L-NMMA, basal releases of epinephrine, norepinephrine and dopamine are increased. 7-Nitroindazole had no effect on basal catecholamine release, suggesting that nitric oxide from an endothelial source was responsible for the inhibition of basal catecholamine release from the adrenal medulla. Epinephrine and norepinephrine releases were augmented when either of the nitric oxide synthase inhibitors was added during submaximal nicotinic stimulation, indicating that endogenous nitric oxide inhibited release of epinephrine and norepinephrine. Both neuronal and endothelial nitric oxide synthases appeared to be responsible for this inhibition. In summary, these studies suggest that nitric oxide, from both neuronal and endothelial sources, modulates evoked catecholamine release from canine adrenal medulla, while nitric oxide from an endothelial source is most likely responsible for modulation of catecholamine release under basal conditions.

Adrenal Medulla↗
PubMed2001

Intrarenal serotonin, dopamine, and phosphate handling in remnant kidneys.

BACKGROUND: Serotonin (5-HT) and dopamine (DA) are intrarenal autocrine/paracrine substances that regulate phosphate reabsorption. The present studies explored intrarenal serotonin and DA metabolism and the implications for phosphate homeostasis in rats with remnant kidneys, a model for renal failure. METHODS: The intrarenal productions of serotonin and DA were determined from measurements of renal interstitial fluid (microdialysate) and urine in rats with remnant or intact kidneys. In clearance studies, the effects of infusion of methiothepin, a serotonin receptor antagonist, or gludopa, a renal selective DA precursor, on phosphate and sodium excretion were determined in rats with a remnant or intact kidneys. RESULTS: Renal interstitial serotonin (5-HT, 3.4 +/- 0.9 pg/min) was fourfold higher than DA (0.6 +/- 0.1 pg/min) in remnant kidneys. Conversely, urinary excretion of serotonin was fourfold less than DA in rats with a remnant kidney (5-HT 0.4 +/- 0.02 vs. DA 1.5 +/- 0.1 ng/min). Infusion of methiothepin or gludopa significantly increased the fractional excretion of phosphate (FE(Pi)) in rats with a remnant kidney from 54 +/- 3 to 67 +/- 7% (P < 0.05) and from 36 +/- 10% to 51 +/- 13% (P < 0.05), respectively. CONCLUSION: We conclude that serotonin preferentially accumulates in the renal interstitium, whereas DA exits primarily via the tubular lumen. Phosphate excretion is increased by both the acute infusion of the serotonin receptor antagonist and the infusion of gludopa, suggesting that both serotonin and DA modulate phosphate excretion in rats with remnant kidneys.

Animals↗
PubMed1999

Endothelin-1 modulates intrahepatic resistance in a rat model of noncirrhotic portal hypertension.

Factors that increase resistance to blood flow through the hepatic sinusoids when portal hypertension occurs in the absence of significant hepatic fibrosis are not completely understood. Experiments were designed to test the hypothesis that endothelin-1 (ET-1) is one of the humoral factors that increases sinusoidal vascular resistance in a bile duct- ligated noncirrhotic portal hypertensive (BDL) rat. The effect of ET-1 and nitric oxide (NO) on contractility of rings of portal vein taken from BDL rats was tested. The effect of ET-1 and NO on intrahepatic resistance in an isolated perfused liver was studied, and localization of ET-1 in the liver was identified by immunohistochemistry. Portal vein rings in BDL rats showed increased maximal tension in response to ET-1, as well as a shift of the dose-response curve to the left as compared with sham-operated animals. Removal of the endothelium further increased contractility. In isolated perfused liver studies, ET-1 increased portal resistance in both sham operated and BDL rats. The endothelin Type A receptor antagonist BQ 123 lowered the high portal resistance in BDL rats to levels comparable with sham operated animals. Infusion of L-arginine lowered resistance to a much smaller extent. In livers from BDL rats, ET-1 was localized in periportal and pericentral hepatocytes and hepatic sinusoidal cells. We conclude that in a BDL model of portal hypertension where distortion of hepatic architecture by fibrosis is minimal, increased resistance to portal blood flow may be mediated by ET-1.

Animals↗
PubMed1999

Dopamine enhances the phosphaturic effect of PTH during acute respiratory alkalosis.

The phosphaturic response to parathyroid hormone (PTH) is blunted during acute respiratory alkalosis. The objective of the present study was to determine the effect of dopamine on the blunted phosphaturic response to PTH during acute respiratory alkalosis. The phosphaturic response to PTH was determined in thyroparathyroidectomized (TPTX) normocapnic and respiratory alkalotic rats in the absence and presence of the infusion of exogenous dopamine (25 microg/kg/min) or of 3,4-dihydroxyphenylalanine (L-DOPA, 250 microg/kg/min) to increase endogenous dopamine synthesis. In normocapnic rats, PTH infusion (33 U/kg plus 1 U/kg/min) significantly increased the fractional excretion of phosphate (FE(Pi)), from 1.5%+/-0.5% to 28.4%+/-4.0%, (deltaFE(Pi) 26.9%+/-4.1%, n = 11, P<.05); in respiratory alkalotic rats, the increase was from 0.4%+/-0.1% to 11.4%+/-1.7% (deltaFE(Pi) 11.0%+/-1.8%, n = 13, P<.05). However, the phosphaturic response to PTH was attenuated in respiratory alkalotic rats (deltaFE(Pi) 26.9%+/-4.1% vs 11.0%+/-1.9%, P<.05). In normocapnic rats, in the presence of dopamine or L-DOPA infusions, PTH infusion significantly increased the FE(Pi) from 6.1%+/-2.3% to 33.4%+/-8.0% (deltaFE(Pi) 27.3%+/-7.0%, n = 5) and from 3.2%+/-0.6% to 32.5%+/-3.3% (deltaFE(Pi) 29.3%+/-3.2%, n = 7), respectively. In respiratory alkalotic rats, in the presence of dopamine infusion, PTH significantly increased the FE(Pi), from 0.6%+/-0.2% to 19.3%+/-3.3% (deltaFE(Pi) 18.7%+/-3.3%, n = 6); in the presence of L-DOPA infusion it increased from 1.0%+/-0.3% to 20.5%+/-2.8% (deltaFE(Pi) 19.5%+/-2.9%, n = 8, P<.05 as compared with PTH alone). Thus the phosphaturic effect of PTH that was attenuated in respiratory alkalotic rats was enhanced by stimulation of endogenous dopamine synthesis by the infusion of L-DOPA.

Acute Disease↗
PubMed1999

gamma-L-glutamyl-L-DOPA inhibits Na(+)-phosphate cotransport across renal brush border membranes and increases renal excretion of phosphate.

BACKGROUND: For treatment of phosphate (Pi) overload in various pathophysiological states, an agent that selectively increases renal Pi excretion would be of major value. Previously, we have shown that dopamine (DA) inhibits Na(+)-Pi cotransport in renal epithelia. However, the administration of DA or its immediate precursor L-DOPA increases DA in multiple tissues. Synthetic dipeptide gamma-L-glutamyl-L-DOPA (gludopa) can serve as an inactive precursor (pro-pro-drug) of DA. This study tested the hypothesis that, because of the unique colocalization of gamma-glutamyltransferase (gamma-GT), aromatic amino acid decarboxylase, Na(+)-Pi cotransporter, and Na(+)-L-DOPA cotransporter in brush border membrane (BBM) of proximal tubular cells, gludopa may elicit phosphaturia by action of DA generated within the kidney. METHODS: Thyroparathyrectomized rats were given placebo, or gludopa, or gludopa + gamma-GT inhibitor acivicin. Urinary excretion of Pi, Ca2+, Na+, K+, DA, cAMP, and cGMP was determined, and Na(+)-Pi cotransport was measured in BBM prepared from kidneys of rats at the end of the experiment. RESULTS: The administration of gludopa resulted in: (a) an inhibition of Na(+)-Pi cotransport, but not cotransport of Na(+)-proline and Na(+)-alanine in BBM; (b) an increase (+300%) of fractional excretion (FE) of Pi and a drop (-35%) of plasma Pi, whereas the plasma levels and FEs of Ca2+, Na+, and K+ were unchanged; (c) an increase in urinary excretion of cAMP. but not cGMP; (d) a 1000-fold increase of urinary excretion of DA, without a change in excretion of norepinephrine; and (e) an incubation of gludopa with BBM in vitro, which caused a release of L-DOPA, and the in vivo administration of acivicin, which blocked actions of gludopa to inhibit Na(+)-Pi cotransport and to increase urinary excretions of Pi and DA. CONCLUSIONS: We conclude that colocalization of enzymes of biotransformation, BBM transporters, and the autocrine/paracrine DA system in cells of proximal tubules constitutes a cellular basis for the potent and specific phosphaturic action of gludopa.

Alanine↗
PubMed1999

Chronic oral L-DOPA increases dopamine and decreases serotonin excretions.

Given the common pathways for uptake and synthesis for dopamine and serotonin, enhanced renal dopamine synthesis in response to increased substrate 3,4-dihydroxyphenylalanine (L-DOPA) is postulated to decrease renal serotonin synthesis. The present study compared the effects of chronic oral administration of L-DOPA on dopamine and serotonin excretion in vivo, with the effects of enhanced dopamine synthesis per nephron due to adaptation to reduced renal mass (RRM). Four groups of rats were studied: sham-operated rats and rats with RRM in the absence and presence of chronic oral L-DOPA. L-DOPA (2 mg. 100 g body wt(-1). day(-1)) for 6-14 days increased calculated dopamine synthesis per nephron in sham-operated rats from 2.0 +/- 0.3 (n = 7) to 13.6 +/- 1.8 pg. day(-1). nephron(-1) (n = 7, P < 0.05) and in rats with RRM from 6.1 +/- 1.3 (n = 7) to 39.3 +/- 5.2 pg. day(-1). nephron(-1) (n = 7, P < 0.05). Chronic oral L-DOPA concomitantly decreased serotonin synthesis per nephron in sham-operated rats (1.6 +/- 0.1 to 1.0 +/- 0.1 pg. day(-1). nephron(-1), n = 7, P < 0.05) and in rats with RRM (5.6 +/- 0.9 to 2.6 +/- 0.4 pg. day(-1). nephron(-1), n = 7, P < 0.05). Both serotonin and dopamine synthesis per nephron were increased in rats with RRM. In conclusion, chronic oral administration of L-DOPA enhances dopamine excretion and decreases serotonin excretion in normal rats and in rats with reduced renal mass. Both dopamine and serotonin excretions per nephron were elevated by renal mass reduction.

Administration, Oral↗
PubMed1997

Opposite paracrine effects of 5-HT and dopamine on Na(+)-Pi cotransport in opossum kidney cells.

Serotonin (5-HT) was recently reported to inhibit cAMP generation in oppossum (OK) cells. We thus investigated the effects of 5-HT upon the Na(+)-Pi cotransport in cultured OK cells and its interactions with dopamine. Incubation of OK cells with 1 nM-10 microM 5-HT resulted in dose-dependent stimulation of Na(+)-Pi contransport (ED50 approximately equal to 8 nM) and also counteracted inhibition of Na(+)-Pi cotransport elicited by dopamine. Pre-incubation with 5-HT decreased cAMP accumulation elicited by forskolin or dopamine and pre-treatment with pertussis toxin abolished both the inhibitory effect of 5-HT upon cAMP levels and stimulation of Na(+)-Pi cotransport. Incubation of OK cells with the 5-HT precursor 5-hydroxytryptophan resulted in time- and dose-dependent accumulation of 5-HT in the medium that also elicited an increase in Na(+)-Pi cotransport. Both the effects of 5-HT and dopamine on Na(+)-Pi cotransport were prevented by carbidopa. The stimulatory effect of 5-HT was specific for the Na(+)-Pi cotransport system since no effects were observed on Na(+)-alanine cotransport. The results indicate that 5-HT stimulates Na(+)-Pi cotransport at least in part via inhibition of cAMP accumulation. We propose that 5-HT and dopamine have opposite actions as paracrine/autocrine regulators of Na(+)-Pi cotransport via opposite effects upon cAMP formation.

5-Hydroxytryptophan↗
PubMed1997

Adrenomedullary secretion of DOPA, catecholamines, catechol metabolites, and neuropeptides.

Catecholamines and their metabolites have been proposed as markers of sympathetic nervous system stimulation. However, the adrenal medulla is a rich source of catecholamines and catecholamine metabolites and may play a significant role in plasma levels of these compounds. In addition to adrenal catecholamine metabolite efflux, the role of the catecholamine precursor 3,4-dihydroxyphenylalanine (DOPA) has not been fully evaluated. The simultaneous effluxes of catecholamines, metabolites, DOPA, and neuropeptides were measured in perfusates from isolated dog adrenals. The relative abundance of compounds detected consistently during unstimulated conditions was epinephrine >> norepinephrine > 3,4-dihydroxyphenylglycol > metanephrine > normetanephrine > dopamine > 3,4-dihydroxyphenylacetic acid > 3-methoxy-4-hydroxyphenylglycol > or = DOPA >> [Met]enkephalin >> neuropeptide Y. Effluxes of analytes were not affected by cocaine and the ratios of catecholamines to metabolites increased dramatically with carbachol stimulation, consistent with negligible reuptake into adrenal cells. Thus, most of the 3,4-dihydroxyphenylglycol is expected to be derived from epinephrine and norepinephrine subsequent to translocation from chromaffin vesicles into the cytosol. The efflux of DOPA increased dramatically during stimulation with 30 microM carbachol in a calcium-dependent manner. Efflux of DOPA during the initial stabilization period of the perfusion preparation declined exponentially, in parallel with the effluxes of the catecholamines and neuropeptides but not with metabolites. Evoked release of DOPA was Ca2+-dependent. These data suggest that DOPA can be stored and released exocytotically from chromaffin granules.

Adrenal Medulla↗
PubMed1996

Nitric oxide reduces basal efflux of catecholamines from perfused dog adrenal glands.

Norepinephrine, epinephrine, dopamine, and both the free and extended forms of [met]enkephalin spontaneously efflux from adrenal glands under basal conditions. The present study was done to determine whether nitric oxide has a regulatory role in these effluxes. Isolated adrenal glands (n = 63) from mongrel dogs were perfused retrogradely with Krebs-Ringer solution. In some experiments NG-monomethyl-L-arginine (3 x 10(-4) M), an inhibitor of nitric oxide synthesis, was added to the perfusate. In other experiments one of the nitric oxide donors, 3-morpholinosydnonimine (10(-7) M or 10(-5) M) or sodium nitroprusside (10(-6) M or 10(-4) M) was added. Norepinephrine, epinephrine, dopamine and their metabolites 3,4-dihydroxyphenylglycol and 3,4-dihydroxyphenylacetic acid in perfusates were quantitated by high performance liquid chromatography with electrochemical detection and in some experiments the [met]enkephalins were determined by radioimmunoassay. In the presence of NG-monomethyl-L-arginine, the basal effluxes of norepinephrine, epinephrine, and dopamine were significantly increased from control, but the effluxes of the free and extended forms of the [met]enkephalins were not changed. The effects of NG-monomethyl-L-arginine on catecholamine efflux were reversed in the presence of L-arginine (10(-3) M). Sodium nitroprusside (10(-6) M) inhibited effluxes of norepinephrine and epinephrine and 3-morpholinosydnonimine had no effect on these effluxes. Dopamine efflux appeared to be under different controls from those of norepinephrine and epinephrine since dopamine efflux was unaffected by sodium nitroprusside and was decreased over time by 3-morpholinosydnonimine (10(-7) M). It is concluded that endogenously produced nitric oxide inhibits the basal efflux of norepinephrine, epinephrine, and dopamine from isolated dog adrenal glands; this inhibition appears to be near maximal for norepinephrine and epinephrine but not for dopamine.

Adrenal Glands↗
PubMed1996

Neuropeptide Y release and contractile properties: differences between canine veins and arteries.

During intense sympathetic activation, as occurs during hemorrhage, veins constrict to a greater degree than do arteries. This study determined if differences in the amounts or actions of the sympathetic cotransmitter neuropeptide Y released from perivascular nerves could contribute to these differences. Strips of canine mesenteric and popliteal arteries and of saphenous and portal veins were superfused, and the releases of noradrenaline and neuropeptide Y evoked by transmural stimulation were assessed. Both compounds were released in greater amounts in the veins than in the arteries. In other experiments rings of each vessel were mounted in organ chambers for isometric-tension recording. Neuropeptide Y (up to 10(-4) M) did not contract any vessel; however, at 3 x 10(-7) M it shifted the frequency-response and concentration-response curves to noradrenaline in the arteries only. In the veins neuropeptide Y had no postsynaptic effect on strong contractions. These results suggest that neuropeptide Y functions locally to affect vasoconstriction of the arteries studied, and may have a different role in the veins. Further, processes involving neuropeptide Y do not appear to account for the differences in responsiveness of these arteries as compared to the veins during intense sympathetic stimulation.

Analysis of Variance↗
PubMed1996

Plasma catechols and monoamine oxidase metabolites in untreated Parkinson's and Alzheimer's diseases.

Prior studies have documented functional and pathological compromise of the peripheral sympathetic nervous system in patients with Parkinson's disease, suggesting the possibility of reduced catecholamine release into the circulation. We measured free plasma catechols in early and untreated patients with Parkinson's disease, but found no evidence of reduced concentrations, compared to control subjects or a group of patients with probable Alzheimer's disease. Rather, there was a significant elevation of plasma norepinephrine within the Parkinson's disease group. Furthermore, 6 of 15 untreated Parkinson's disease patients (40%) displayed markedly elevated plasma concentrations of the catecholamine MAO metabolites, DOPAC or DOPEG. Despite this finding, platelet MAO-B activity measured in these and all other Parkinson's disease patients fell well within the range of the control subjects, and was also statistically similar to the group with Alzheimer's type dementia. Plasma dopa levels were similar in all groups, whereas the majority of patients in the three groups had plasma free dopamine and epinephrine concentrations below the limits of detection. These trends toward increased, rather than decreased, circulating catechol concentrations suggest that peripheral sympathetic nervous system catecholamine production and release is not severely compromised in patients with early Parkinson's disease. In addition, we were unable to confirm certain previous reports of elevated MAO-B activity in patients with Parkinson's or Alzheimer's diseases.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Norepinephrine release during vasoconstriction induced by cross-linked hemoglobin.

The pressor effect of hemoglobin-based blood substitutes is due partly to their capacity to scavenge nitric oxide (NO), a potent vasodilator. NO also appears to modulate the release of norepinephrine (NE) from sympathetic nerve endings in some blood vessels. Thus studies were designed to determine if contraction occurring in response to alpha alpha-cross-linked hemoglobin (XL-Hb) is due in part to increased exit of NE from vascular nerve endings. Helical strips of canine femoral artery were superfused in vitro with Krebs-Ringer solution and, for each strip, the overflow of NE into the superfusate as well as contractile responses were measured concurrently during basal conditions, during nerve stimulation and during tyramine-evoked release of NE. XL-Hb (10 microM) contracted unstimulated strips without affecting NE overflow. NE overflow also was unchanged by NG-monomethyl-L-arginine (L-NMMA; 300 microM), an inhibitor of NO synthesis; by sodium nitroprusside (SNP; 1 microM) an NO donor; by a combination of XL-Hb and L-NMMA; or of XL-Hb and SNP. These treatments contracted the strips to the same degree as did XL-Hb alone, except for SNP, which induced relaxation. Transmural stimulation of the strips at 2 and 10 Hz induced NE overflow and contraction, neither of which was affected by any treatment except SNP which significantly (P < 0.05) increased NE overflow while inhibiting contraction. In other experiments, XL-Hb augmented contractions induced by tyramine (10 microM) although the resulting NE release was unaffected. These results suggest that, in the femoral artery, contractions induced by XL-Hb are not due to increased efflux of NE from vascular nerve endings but are consistent with inhibition of the the actions of NO.

Animals↗
PubMed1996

Releases of norepinephrine and dopamine in ventriculocisternal perfusions in hepatectomized and laparotomized rats.

The completely hepatectomized rat has frequently been used as a model to study changes in the economy of norepinephrine (NE) and dopamine (DA) in hepatic coma. Hypothermia characteristically develops in hepatectomized rats and also occurs in patients in hepatic coma and is associated with improved survival in both. The aims of the present study were to measure both release and uptake of NE and release of DA in brain in warm (37 degrees C) and cool (30-32 degrees C) rats at 3-5 h after laparotomy or hepatectomy. Ventriculocisternal perfusions of the brain were performed on rats under basal conditions and during releases evoked by 40 mM K+. Basal releases of NE and DA and evoked release of DA were greater in the warm hepatectomized rats than in all other groups. In some studies, 10(-5) M amitriptyline was added to the perfusates to assess whether neuronal uptake was changed after hepatectomy. Uptake of released NE was equally robust in cool hepatectomized as in cool laparotomized rats but could not be measured in warm hepatectomized rats because of amitriptyline toxicity in these rats. Decreases in NE and increases in DA content were found in most areas of the brain after perfusion. Increased releases of NE and DA may contribute to the pathogenesis of hepatic encephalopathy.

Animals↗
PubMed1996

Levodopa and deprenyl treatment effects on peripheral indices of oxidant stress in Parkinson's disease.

The oxidant stress theory of Parkinson's disease (PD) hypothesizes that levodopa treatment may be potentially harmful and this is supported by studies demonstrating levodopa toxicity to cultured dopaminergic neurons. These in vitro experiments, however, lack the physiologic protective mechanisms present in vivo. Oxyradical damage to cell membranes liberates malondialdehyde, which we measured in the serum of 27 PD patients just before and after levodopa (with carbidopa) administration. We also measured plasma products of the two routes by which levodopa potentially generated oxyradicals: (1) 5-S-cysteinyl-dopa (derived from levodopa autoxidation), and (2) 3,4-dihydroxyphenylacetic acid (DOPAC), produced by monoamine oxidase (MAO) metabolism of dopamine. Following levodopa/carbidopa administration, both of these plasma products were markedly increased; however, the mean serum malondialdehyde concentration was unchanged and remained similar to the normal control group (N=15) value. Chronic treatment with the MAO-B inhibitor, deprenyl (N=16), was not associated with any differences in serum malondialdehyde or plasma 5-S-cysteinyl-dopa concentrations compared with those not treated with deprenyl (N=11). The post-levodopa rise of plasma DOPAC was only slightly attenuated with deprenyl therapy, consistent with a predominant MAO-A effect in the circulation and peripheral organs. Thus, in contrast to in vitro studies, we did not detect evidence of oxidative damage in the circulation following levodopa administration, despite marked increase in the products of dopamine oxidative metabolism.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Lowered norepinephrine turnover as a sign of impaired ganglionic transmission after preganglionic lesioning by acetylcholinesterase antibodies.

Monoclonal antibodies to acetylcholinesterase are known to destroy preganglionic sympathetic terminals in rats. To investigate resulting changes in sympathetic tone, turnover of norepinephrine (NE) was examined in five adrenergically innervated tissues: submaxillary salivary gland, heart, spleen, vas deferens and kidney. At time zero, 50 mu Ci of [3H]NE was injected into the tail vein; turnover rates were determined from the loss of radioactive NE between 2 and 24 hr later. Experiments with ganglionic blocking agents showed that most NE turnover was related to impulse traffic. Combined treatment with atropine (4 mg/kg/day) and chlorisondamine (20 mg/kg/day) reduced the apparent turnover rate constant by two thirds or more in all organs except vas deferens. NE turnover was likewise slowed after treatment with acetylcholinesterase antibodies (1.6 mg i.v., 5 days earlier): apparent rate constants fell 50% or more in submaxillary gland, heart and kidney. The reduced NE turnover in these end organs suggested that preganglionic immunologic lesions blocked synaptic transmission in the respective sympathetic ganglia. Sustained turnover in the spleen, however, suggested that certain pathways through the celiac ganglion resisted immunologic lesion or recovered quickly. Hence, there may be structural or functional differences among the sympathetic ganglia, especially between pre- and paravertebral groups.

Acetylcholinesterase↗
PubMed1995

No evidence for systemic oxidant stress in Parkinson's or Alzheimer's disease.

Oxidant stress secondary to dopamine metabolism has been proposed as a pathogenic factor in the development of Parkinson's disease. Biochemical abnormalities extending beyond the central nervous system have been identified in patients with this condition. Previous investigators have found abnormally elevated concentrations of the lipid peroxidation product, malondialdehyde, in the plasma and serum of patients with Parkinson's disease. We attempted to replicate these findings but controlled for other factors that could influence malondialdehyde levels. We detected no significant elevations in mean serum malondialdehyde concentrations in either levodopa-treated or untreated patients with Parkinson's disease, compared to normal controls; similarly, no elevation was found in a group of patients with dementia of Alzheimer's type. On the other hand, a group of subjects with diabetes mellitus but no neurodegenerative disease had significantly elevated mean serum malondialdehyde levels, consistent with previous studies of diabetic patients. Autoxidation is one of the two major routes by which dopamine and dopa metabolism may generate oxygen free radicals. We analyzed the autoxidation product of dopa, 5-S-cysteinyl-dopa, in the plasma of these same groups of patients with neurodegenerative disease and normal controls; no significant differences were identified. Serum concentrations of two other antioxidant substances, alpha-tocopherol and uric acid, were also statistically similar in these groups. In conclusion, analysis of several blood products relevant to oxidant stress, including malondialdehyde, 5-S-cysteinyl-dopa, alpha-tocopherol, and uric acid, failed to distinguish patients with Parkinson's disease or dementia of Alzheimer's type from controls.

Aged↗
PubMed1995

Effluxes of 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenylglycol, and norepinephrine from four blood vessels during basal conditions and during nerve stimulation.

Effluxes of 3,4-dihydroxyphenylalanine, 3,4-dihydroxyphenyglycol, and norepinephrine from four superfused canine blood vessels (saphenous and portal veins and mesenteric and pulmonary arteries) were studied under basal conditions and during nerve stimulation. From quantification of the compounds a series of indices of activities at neuroeffector junctions are proposed. These are (a) basal overflow of 3,4-dihydroxyphenylglycol as an index of vesicular-cytoplasmic translocation of norepinephrine, (b) the increase in 3,4-dihydroxyphenyglycol overflow attributable to nerve stimulation as an index of neuronal reuptake of norepinephrine released by stimulation, (c) the sum of the increases in overflows of norepinephrine and 3,4-dihydroxyphenylglycol attributable to nerve stimulation as an index of evoked release of norepinephrine, and (d) the efflux of 3,4-dihydroxyphenylalanine as an index of the activity of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of norepinephrine. There were clear differences between these indices in the vessels. Correlation coefficients of the indices among vessels indicated that a high tissue norepinephrine level was associated with high biosynthetic capacity and high vesicular-cytoplasmic exchange but not with high release. There was no evidence suggesting feedback inhibition of synthesis by neuroplasmic norepinephrine--whether arising from vesicular-cytoplasmic translocation or from reuptake from the junctional cleft. The major value of these indices will probably be in determining the integrated effects of pharmacologic agents at neuroeffector junctions in different blood vessels.

Animals↗