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Biomedical subjects

A Witter

Publications and source records attributed to A Witter.

At least 19 recordsLinked to original sources
PubMed2005

Trifluoroacetate profiles in the Arctic, Atlantic, and Pacific Oceans.

A series of depth profiles was collected at 22 sites in the Arctic, North and South Atlantic, and Pacific Oceans to determine spatial patterns for trifluoroacetate (TFA) concentrations in the marine environment and to investigate possible natural sources of TFA. Profiles were also taken over underwater vents in the North and South Pacific and the Mediterranean Sea. At the profile sites, TFA values ranged from <10 ng/L in the Pacific Ocean to greater than 150 ng/L in the Atlantic Ocean. Samples from the Canada Basin of the Arctic Ocean exhibited variable TFA concentrations (60-160 ng/L) down to 700 m. Below this depth, in water having 14C ages exceeding 1000 years, the TFA concentrations were constant (150 ng/L). Water returning to the Atlantic through the Canadian Arctic Archipelago had constant high TFA values. Profiles from the Northern Atlantic exhibited high values at all depths but were more consistent in the Western Atlantic. The northwestern Pacific Ocean surface profile sites exhibited low TFA concentrations in the top 100 m increasing to a maximum of 60 ng/L with depth. Samples from the South Pacific Ocean site had generally low values with a few depths (>800 m) having concentrations of 50 ng/L or more. To determine if underwater vents could contribute to the TFA concentrations in the oceans, profiles were taken over three vents in the Pacific and Mediterranean Oceans. The results suggest that some deep-sea vents may be natural sources of TFA.

Arctic Regions↗
PubMed2001

Metal-organic complexation in the marine environment.

We discuss the voltammetric methods that are used to assess metal-organic complexation in seawater. These consist of titration methods using anodic stripping voltammetry (ASV) and cathodic stripping voltammetry competitive ligand experiments (CSV-CLE). These approaches and a kinetic approach using CSV-CLE give similar information on the amount of excess ligand to metal in a sample and the conditional metal ligand stability constant for the excess ligand bound to the metal. CSV-CLE data using different ligands to measure Fe(III) organic complexes are similar. All these methods give conditional stability constants for which the side reaction coefficient for the metal can be corrected but not that for the ligand. Another approach, pseudovoltammetry, provides information on the actual metal-ligand complex(es) in a sample by doing ASV experiments where the deposition potential is varied more negatively in order to destroy the metal-ligand complex. This latter approach gives concentration information on each actual ligand bound to the metal as well as the thermodynamic stability constant of each complex in solution when compared to known metal-ligand complexes. In this case the side reaction coefficients for the metal and ligand are corrected. Thus, this method may not give identical information to the titration methods because the excess ligand in the sample may not be identical to some of the actual ligands binding the metal in the sample.

Journal Article↗
PubMed1984

Muscarinic cholinergic receptors in peripheral lung tissue of normal subjects and of patients with chronic obstructive lung disease.

Muscarinic cholinergic receptors have been identified and characterized by radioligand binding studies in human peripheral lung tissue. The tissue was obtained at thoracotomy of 12 patients, of whom four had chronic obstructive lung disease. The radioligand 1-quinuclidinyl [phenyl-4-3H]benzilate (3H-QNB) was used to label the muscarinic cholinergic receptors. Binding was saturable, protein dependent and showed a high affinity and stereospecificity. Specific binding could be inhibited by agonists and antagonists; molar inhibition constants determined for the agents used were of the same order of magnitude as those reported for 3H-QNB inhibition in various tissues of laboratory animals. Inhibition experiments with agonists resulted in Hill slopes which were significantly different from unity, indicating multiple binding sites. The stable GTP analogue guanyl-5'-imidodiphosphate had no effect on the Hill slopes of agonists or antagonists. The number of binding sites was significantly less in lung tissue from patients with chronic obstructive lung disease.

Aged↗
PubMed1983

In vivo interaction of gamma-type endorphins with dopaminergic ligands in rat brain.

The beta-endorphin (beta E) fragment des-Tyr1-gamma-endorphin (DT gamma E, beta E-(2-17)) has been reported to interact with neuroleptic binding in vivo but not in vitro. We have attempted to replicate the in vivo experiments and extended the work to include conditions in which des-enkephalin-gamma-endorphin (DE gamma E, beta E-(6-17)) exhibited behavioral activity. Systemically administered haloperidol significantly elevated plasma and decreased striatal [3H]spiperone. DE gamma E significantly elevated plasma [3H]apomorphine when both substances were injected directly into the nucleus accumbens. gamma-type endorphins consistently but non significantly decreased brain spiperone or apomorphine binding. It is concluded that the interaction between gamma-type endorphins and dopaminergic binding sites may be either indirect or limited to a subset of these sites.

Animals↗
PubMed1983

Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF.

The penetration of neurohypophyseal peptides after peripheral administration into the cerebrospinal fluid (CSF) was studied in freely moving rats. In addition, the clearance of these peptides from CSF was investigated. Increased concentrations of vasopressin (AVP) in CSF were detectable 2 min after s.c. injection of 5.0 micrograms of this peptide. Peak concentration was reached at 5 min after administration and this level declined slowly over the next hour. Administration of 5.0 micrograms oxytocin (OXT) s.c. or i.v. resulted in increased OXT levels in CSF within 10 min after application. After 60 min a significant elevation of OXT in CSF was no longer present. These data reveal that approximately 0.002% of the peripherally applied amount of AVP or OXT reached the central nervous system at 10 min after injection. AVP (2.5 ng) and OXT (5.0 ng) applied into one of the lateral brain ventricles reached the cisternal cavity within 2 min after administration. Both neuropeptides were cleared from the CSF with terminal half-times of 26 and 19 min for AVP and OXT, respectively. The present data demonstrate that neurohypophyseal hormones do cross the blood-brain barrier in amounts obviously sufficient to induce central actions.

Animals↗
PubMed1983

Adrenocorticotropin: ACTH1-38 is a major product of biotransformation by brain synaptic membranes.

Since adrenocorticotropic hormone is found in the brain, and several of its fragments affect adaptive behavior, the formation of fragments of ACTH1-39 by a rat brain synaptic membrane fraction was investigated. Following the incubations at physiological pH conditions, the digests were fractionated by HPLC to quantitate the amounts of ACTH1-39 remaining and products formed. Time- and enzyme-dependent disappearance of ACTH1-39 was accompanied by the accumulation of a major peptide metabolite (product B). Amino acid analysis and NH2-terminal end-group determination revealed that product B was identical to ACTH1-38. These results indicate the predominance of carboxypeptidase activity in the degradation of ACTH1-39 by brain synaptic membranes.

Adrenocorticotropic Hormone↗
PubMed1982

Interaction of calcium with 3H-morphine binding to synaptosomes of the guinea-pig ileum.

Specific binding sites for 3H-morphine were assayed in subcellular fractions of a crude mitochondrial P2 pellet from the guinea-pig ileum longitudinal muscle-myenteric plexus, prepared by discontinuous sucrose-gradient fractionation. The highest specific binding (ca. 100 fmol/mg protein) was obtained in the fraction containing synaptosomes, as examined by electron microscopy. A synaptosomal fraction prepared from guinea-pig brain had comparable specific binding (ca 130 fmol/mg) to that of the ileal synaptosomal fraction. Addition of calcium (10 mM) to the binding assay medium resulted in a marked decrease in particular of the specific 3H-morphine binding. Detailed analysis of the specific 3H-morphine binding. Detailed analysis of the specific 3H-morphine binding in the synaptosomal fraction of the ileum revealed that 1) a saturable component of specific opiate binding was present between 0.34 and 21.74 nM of 3H-morphine; 2) in the presence of 3 and 10 nM of calcium similar decreases of specific 3H-morphine binding were obtained, indicating that this binding was maximally inhibited already by 3 mM of calcium; 3) both in the absence and presence of calcium the KD of specific 3H-morphine binding was about 38 nM, indicating a non-competitive nature of the calcium inhibition; 4) addition of magnesium exhibited a similar effect as that of calcium, although magnesium appeared to be less potent than calcium in this respect. The data are discussed in the context of previously observed calcium effects on opioid actions in the electrically stimulated guinea-pig ileum bioassay and may contribute to the evidence that the interaction of calcium and opioids on the stimulus-release coupling mechanism at the neuromuscular junction of the guinea-pig ileum is occurring beyond opioid receptor activation as well.

Animals↗
PubMed1982

H-Pro-[3H]Leu-Gly-NH2: plasma profile and brain uptake following subcutaneous injection in the rat.

Following subcutaneous injection of the tripeptide H-Pro-[3H]Leu-Gly-NH2 ([3H]PLG) in rats, the profile of intact peptide and its radioactively labeled metabolites was examined both in plasma and in brain tissue. [3H]PLG and metabolites were determined in trichloroacetic acid extracts by reverse-phase paired-ion HPLC. Maximal plasma levels of unmetabolized PLG were reached 6-8 min after administration, after which they decreased with an elimination half-life of 20 min. The uptake of [3H]PLG in the brain ranged from 0.0013% to 0.0017% of the administered dose per g tissue at 6-30 min following subcutaneous injection. After comparing these results with our previous findings with intravenous injection of [3H]PLG, it seemed likely that the subcutaneous route of administration might be more effective in eliciting CNS effects of PLG than the intravenous route of administration. The metabolite profiles in plasma and brain point to an initial cleavage of PLG at the NH2-terminal side and a very rapid degradation of the peptide intermediate H-Leu-Gly-NH2.

Animals↗
PubMed1982

H-Pro-[3H]Leu-Gly-NH2: uptake and metabolism in rat brain.

The uptake and metabolism of H-Pro-[3H]Leu-Gly-NH2 ([3H]PLG) in rat brain was investigated by reverse-phase paired-ion high pressure liquid chromatography. Following in vitro incubation of [3H]PLG with rat brain subcellular preparations, the microsomal-cytosol fraction was about twice as active in degrading PLG as the crude mitochondrial-synaptosomal fraction. For both enzyme preparations the pH optimum was found at pH 7-7.5. The major labeled metabolite was [3H]leucine, whereas 3H]labeled Leu-Gly-NH2 as the only labeled peptide intermediate was found in trace amounts. After intravenous injection of [3H]PLG the uptake of unmetabolized peptide in the brain appeared to be very low: 0.008% and 0.001% of the administered dose/g tissue at 2 and 5 min after injection respectively, while at longer survival times intact peptide was below the detection limit. Compared with the intravenous route of administration, intracerebroventricular injection of [3H]PLG yielded much higher brain concentrations of unmetabolized PLG. Following both routes of administration, the metabolite profile was in agreement with that obtained after in vitro incubation. However, the in vivo experiments also showed considerable incorporation of [3H]leucine liberated from [3H]PLG into proteins. Both the in vitro and in vivo results indicate that the initial cleavage of PLG in rat brain occurs at the NH2-terminus and that the dipeptide intermediate H-Leu-Gly-NH2 is subsequently hydrolyzed to its constituent amino acids very rapidly.

Animals↗
PubMed1981

Gamma-melanotropin and brain function.

In view of the close structural similarity between the pro-opiocortin fragment, gamma-MSH, and ACTH/MSH-type peptides, the behavioural profile of gamma-MSH was explored. Attention was first focused on behavioural procedures in which ACTH/MSH-related neuropeptides have been found effective. It was found that gamma-MSH and ACTH-like neuropeptides had opposite effects on avoidance behaviour. In this respect the activity of gamma-MSH resembles that of opiate antagonists rather than that of beta-endorphin. Accordingly, ACTH(1-24) induced excessive grooming which is blocked by opiate antagonists and is attenuated by gamma-MSH. In addition, gamma-MSH injected into the periaqueductal grey matter of the brainstem of opiate-naive rats elicited symptoms reminiscent of those seen after opiate withdrawal. Gamma-MSH attenuated several effects of intracerebroventricularly administered beta-endorphin (e.g. antinociception, hypothermia, alpha-MSH release) and decreased the acquisition of heroin self-administration. Although gamma-MSH at rather high doses displaced naloxone from its specific binding sites in brain homogenates, it did not interfere with beta-endorphin-induced effects on in vitro muscle preparations (guinea-pig ileum; rat rectum). Interestingly, gamma-MSH induced relaxation of the rat rectum in vitro. It is postulated that gamma-MSH may attenuate beta-endorphin-induced effects by acting via gamma-MSH receptor sites (functional antagonism), although a pharmacological antagonism cannot be excluded as yet.

Adrenocorticotropic Hormone↗
PubMed1980

H-Pro-[3H]Leu-Gly-NH2: metabolism in human and rat plasma investigated by high-pressure liquid chromatography.

H-Pro-Leu-Gly-NH2 (PLG) was labeled with 3H-leucine by catalytic tritiation of H-Pro-methylallylgylcyl-Gly-NH2 and purified by ion-exchange chromatography. Metabolism of 3H-PLG in rat and human plasma was investigated by reversed phase-paired ion high-pressure liquid chromatography. All possible metabolites could be completely separated within 25 min. Half-lives, based on disappearance of intact 3H-PLG, for in vitro metabolism were 26.4 min (rat) and 5.6 days (human). The only significant metabolite was 3H-leucine. A rate-limiting, species-specific enzyme seems responsible for the initial breakdown of PLG. Disappearance of 3H-PLG from rat plasma, following i.v. administration, proceeded with half-lives of 1.03 min (distribution) and 9.8 min (elimination).

Animals↗
PubMed1980

On the presence of receptors for ACTH neuropeptides in the brain.

There is considerable evidence, based on a variety of CNS effects and structure-activity relations as well as on indirect receptor studies, for the presence of multiple binding sites for ACTH neuropeptides in the CNS. Mainly because of the very low effective CNS concentrations of these peptides, putative CNS receptors seem characterized by very high affinity and very low capacity. These properties interfere with the demonstration of such receptor sites by direct binding assays using 3H-peptides and seem to necessitate the use of labeled neuropeptides with considerably higher specific activities.

Adenylyl Cyclases↗
PubMed1977

Specific uptake of a behaviorally potent [3H]ACTH4-9 analog in the septal area after intraventricular injection in rats.

Distribution within the brain of a behaviorally potent [3H]ACTH4-9 analog 2 h after intraventricular injection in rats was studied in the presence and absence of behaviorally and structurally similar peptides, to explore the significance of earlier found preferential uptake of the [3H]ACTH4-9 analog in the septal area. Hypophysectomy resulted in significantly enhanced uptake of radioactivity in the septum as compared to normal rats. No increase in this brain area of hypophysectomized rats was observed after intraventricular injection of [3H]Phe. Elevated circulating ACTH levels after adrenalectomy seemed too low to compete with the septal uptake of the ACTH4-9 analong. Subcutaneous substitution of hypophysectomized rats with sustained release zinc phosphate preparations of the behaviorally equipotent peptides ACTH1-24 and ACTH4-10 decreased the accumulation of the [3H]ACTH4-9 analog in the septum, whereas treatment with the behaviorally inactive fragment ACTH11-24 is not effective. Retreatment of hypophysectomized rats with neuropeptides, differing structurally from natural ACTH peptides (7-D-Phe-ACTH4-10, BETA-LPH61-76 and 9-desglycinamide, 8-Lys-vasopressin), did not change the uptake of the ACTH4-9 analog in any of the investigated brain areas. These results give evidence for specific uptake of the ACTH4-9 analog in the septal region, because competitive displacement occurs only with peptides which both behaviorally and structurally are closely related to the ACTH4-9 analog.

Adrenalectomy↗