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W J Shoemaker

Publications and source records attributed to W J Shoemaker.

At least 37 records · Page 2Linked to original sources
PubMed1990

Characterization of kappa opioid binding using dynorphin A1-13 and U69,593 in the rat brain.

Previous studies of kappa opioid binding sites have suggested heterogeneous binding to this class of opioid receptors. To further investigate kappa receptor heterogeneity, we analyzed the binding properties of various "kappa-selective" ligands in rat brain homogenates. Displacement assays were carried out using [3H]bremazocine in the presence of various displacing ligands under mu and delta receptor-blocked conditions. Homologous displacement of [3H]bremazocine produced "shallow" displacement which best fit a two-site model of drug-receptor interaction. Dynorphin A1-13 and U69,593 exhibited similar biphasic displacement of [3H]bremazocine. Maximal displacement by these ligands, however, represented only approximately 55% of total [3H]bremazocine binding, which suggests the existence of a third component of [3H]bremazocine binding. Biphasic displacement by dynorphin A1-13 was detected in tissue throughout the brain and the spinal cord, whereas the dynorphin-resistant component of [3H]bremazocine binding was uniquely absent in the spinal cord. U50,488H, tifluadom and ethylketocyclazocine appeared to displace from additional, dynorphin-insensitive sites, as their maximal displacement exceeded that seen with either dynorphin A1-13 or U69,593. These results strongly suggest the existence of at least three components of non-mu, non-delta [3H]bremazocine binding in the rat brain: two with differential affinity for dynorphin A1-13 and U69-593 (kappa-1 and kappa-2 sites), and a third (termed here R1) that was further resolved into two binding sites by bremazocine. Preliminary analysis of the R1 component using naloxone revealed one high-affinity site, which may be opiate in nature, and a second site whose binding properties closely resemble those of the sigma receptor described by others.

Analgesics↗
PubMed1986

Subcutaneous administration of behaviorally effective doses of arginine vasopressin change brain AVP content only in median eminence.

The accumulation of [8-arginine]vasopressin (AVP) in brain areas inside the blood-brain barrier (thalamus-hypothalamus, amygdala with overlying temporal cortex, hippocampus and cerebral cortex) and outside the blood-brain barrier (median eminence of the hypothalamus and area postrema) was measured after subcutaneous injection of the hormone. The plasma concentrations of AVP peaked at 5 min after subcutaneous injection and declined in a biphasic manner over the next 115 min. The concentration of AVP in brain tissue samples peaked at 20 min after the subcutaneous injection of AVP; the decline of AVP in the areas protected by the blood-brain barrier followed the time course seen for plasma. The concentration of AVP in the brain areas not so protected also peaked at 20 min but these declined at rates that differed from other brain areas and plasma. The concentration of AVP in the plasma and in most brain areas depended on the dose administered, while those in the median eminence and in the area postrema did not. Water deprivation for 24 and 48 h significantly elevated both the plasma AVP concentration and the concentration of AVP in the hypothalamus and in the amygdala-temporal cortex samples. The increases in AVP after water deprivation are limited to these two regions and are quantitatively much lower than after peripheral administration. Furthermore, when the brains of anesthetized rats were perfused free of blood, there were no changes in regional brain AVP content after subcutaneous treatment with 5,000 ng/kg of AVP, except for the median eminence. These data suggest that circulating AVP does not enter the parenchyma of brain areas protected by the blood-brain barrier in sufficient quantities to be detected by our assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Senescent change in tissue weight and immunoreactive beta-endorphin, enkephalin, and vasopressin in eight regions of C57BL/6J mouse brain and pituitary.

Tissue weights and immunoreactive (IR) content and concentration of beta-endorphin, enkephalin, and vasopressin were assayed for senescent change in anterior pituitary, neurointermediate pituitary, hypothalamus, hippocampus, striatum, dorsolateral cortex, and pons-medulla, as well as residual brain samples remaining after the other dissections. Groups of naive male C57BL/6J mice, 8-12 months old and 28-32 months old, served as subjects. Old mice exhibited significant decline in anterior pituitary and hippocampus weight. Significant increases with age were found in pons-medulla weight. IR beta-endorphin content decreased in hypothalamus and neurointermediate pituitary. IR enkephalin decreased in striatum and dorsolateral cortex. IR vasopressin content increased in hypothalamus and residual brain. Assays were replicated in later experiments using additional subjects, for total Ns of up to 54 mice. Although significant overall results were always consistent in direction from replication to replication, the magnitude of age change exhibited considerable variability. Such results suggest that single experiments on age changes in neuropeptides, particularly those giving negative results, should be carefully scrutinized and replicated before their acceptance as evidence for a transmitter's stability or instability throughout the lifespan.

Aging↗
PubMed1985

Characterization of the prodynorphin and proenkephalin neuropeptide systems in rat hippocampus.

Opioid peptides derived from prodynorphin were localized immunocytochemically to dentate granule cells and mossy fibers of the rat hippocampus with antisera against dynorphin A(1-17) and dynorphin B. Extracts of microdissected hippocampal regions were resolved by reverse phase and molecular exclusion chromatography to identify the molecular forms of the dynorphin A immunoreactivity and to quantify regional contents. Results demonstrated that the relative concentration of dynorphin A within each dissected region of hippocampus agreed well with the distribution of dynorphin A detected by immunocytochemical methods. Immunostaining of proenkephalin-derived opioid peptides, [Leu5]enkephalin and bovine adrenal medullary peptide-22P, was concentrated in cell bodies of the entorhinal cortex, nerve fibers in the perforant pathway, and terminals in the outer molecular layer of the dentate gyrus. Light immunostaining of granule cells and mossy fibers with these antisera was also found. The relative concentration of [Leu5]enkephalin immunoreactivity in each microdissected region of the hippocampus also agreed well with the distribution of [Leu5]enkephalin immunostaining. Chromatography of hippocampal regional extracts demonstrated that the immunoreactivity measured was due to the presence of authentic [Leu5]enkephalin. The probable neurotransmitter function of both [Leu5]enkephalin and dynorphin A was shown by their calcium-dependent release after in vitro depolarization of hippocampal tissue. The reported presence of beta-endorphin in hippocampus was not verified. Comparison of the hippocampal distribution and content of prodynorphin and proenkephalin-derived opioids suggests that separate populations of neurons containing these two peptide families form distinct neurotransmitter systems of roughly equal concentration.

Animals↗
PubMed1984

Developmental changes in rat liver alcohol dehydrogenase.

Hepatic alcohol dehydrogenase activity and mass content change coordinately during development in male rats. Enzyme activity and mass content increase continuously after birth to 100 and 80% of maximal values within 6 weeks (2.6 +/- 0.4 mumole/min/g liver and 92 +/- 20 micrograms/g liver), respectively. When expressed per milligram of soluble proteins, both parameters peak at 3 weeks (0.052 +/- 0.002 mumole/min/mg protein and 2.0 +/- 0.4 micrograms/mg protein) and then decrease gradually to plateau levels. These decreases probably arise from a "surge" in soluble liver protein levels that occurs after weaning. Similar developmental patterns also occur in female rats. These findings are the first quantitative measurements of this enzyme in developing animals.

Aging↗
PubMed1983

Effect of 6-hydroxydopamine lesions on norepinephrine-induced [3H]glycogen hydrolysis in mouse cortical slices.

The effects of norepinephrine (NE) on in vitro [3H]glycogenolysis were assessed in slices of cerebral cortex from mice whose cortical noradrenergic innervation had been severely reduced by intracisternal 6-hydroxydopamine (6-OHDA) injections. A supersensitive response to NE was observed, as demonstrated by a decrease in the EC50 of the catecholamine in the lesioned mice from 533 +/- 88 nM to 39.3 +/- 7.9 nM. This supersensitive response, observed two weeks after the lesion, was post-synaptic since isoproterenol, a beta-adrenergic agonist not accumulated by pre-synaptic uptake mechanisms, also gave an equally supersensitive response.

Adrenergic Fibers↗
PubMed1983

Chemical and physiological aspects of the actions of lithium and antidepressant drugs.

The possible mechanisms underlying the anti-manic actions of lithium have been examined in a variety of interdisciplinary experiments. The possibility that lithium can regulate the sensitivity changes in dopaminergic transmission produced by chronic treatment with haloperidol has been tested. Although a modest modification of behavioral responses to the dopamine agonist apomorphine was found, there was no evidence that this action of lithium reflected alterations of the binding parameters of dopamine-related ligands. In other studies, consistent, dose-dependent increases in brain enkephalin content were found after rats consumed a specially manufactured lithium diet for 2-3 weeks. Not only were brain enkephalin levels increased after this treatment, but some signs of basal analgesic responsiveness also suggested that the elevated levels of enkephalins were functionally significant. To test the possibility that the effects of lithium may not be seen in normal rats, the effects of lithium were compared on spontaneously hypertensive and unaffected, normotensive rats of a related strain. Treatment with lithium altered blood pressure in the hypertensive strain but did not affect blood pressure in the controls. These studies suggest that multiple brain systems may be regulated by treatment with lithium but that the critical pathophysiological process may not be demonstrable in the normal rat.

Animals↗
PubMed1983

Comparison of liver alcohol dehydrogenases in Fischer-344 and Sprague-Dawley rats.

Livers of Sprague-Dawley rats contain 30-100% more alcohol dehydrogenase activity than livers of Fischer-344 rats. When weight-matched rats from both strains are injected with the same dose of ethanol (1.2 g/kg), Sprague-Dawley rats achieve lower blood alcohol levels than Fischer-344 rats at all the time-points tested. Purified alcohol dehydrogenases from both strains of rats exhibit identical electrophoretic mobilities in SDS-polyacrylamide Section and in isoelectric focusing slab gels, pH optima, peptide maps, Km for ethanol, and capacities to bind monospecific rabbit antibodies. Quantitative differences in alcohol dehydrogenase activity between these strains of rats are due to differences in their liver alcohol dehydrogenase levels.

Alcohol Dehydrogenase↗
PubMed1983

Methodological considerations in culturing peptidergic neurons.

Both explant and dispersed cell culture preparations of brain tissue provide a means to directly assess the functions of neuropeptide-containing brain cells isolated from the complex influences present in vivo. The validity of the approach depends on reproducibility of observations. In dispersed cell cultures, we find that cell responses, as determined by secretion of the peptide somatostatin, have remained relatively constant both quantitatively and qualitatively over numerous preparations. In addition, for pharmacologic studies on somatostatin secretion, data from several laboratories are in good agreement. The validity of the dispersed cell approach also depends on whether the pharmacologic and physiologic behavior of cells parallels that expected of excitable tissue. The variability of the explant cultures from culture dish to culture dish makes quantitative experiments, such as demonstrated with the dispersed cultures, difficult. On the other hand, explant cultures better maintain the integrity of the tissue components, so that interactions between neurons and glial cells could occur as in vivo. The long-term health and viability of neuropeptidergic cells in explant and dispersed culture make both preparations potentially useful models to examine central nervous system physiology. Future work with such preparations must eventually address the problems of culturing adult brain tissue, the precise nutrient and hormonal requirements of brain cells, so that undefined medium components, such as serum, can be eliminated from the culture environment, and the general question of whether observations made in vitro facilitate our understanding of intact brain physiology.

Animals↗
PubMed1982

Effects of chronic lithium treatment on dopamine receptors in the rat corpus striatum. I. Locomotor activity and behavioral supersensitivity.

Spontaneous locomotor activity and dopaminergic responsivity were assessed after long-term dietary treatment with the anti-manic drug lithium. Chronic dietary Li administration was not accompanied by the toxicities often reported with other modes of administration. In addition, the diet reliably yields serum and brain Li levels in the prophylactic range for manic-depressive illness. After 4 weeks exposure to Li, spontaneous locomotor activity was reduced as compared to subjects on the control diet whether or not food intake was restricted. The depression of locomotor activity following an injection of the dopamine agonist, apomorphine, was less severe in animals that ingested Li compared to those with free access to the control diet. Finally, in confirmation of the findings of Pert et al., chronic Li administration led to a partial attenuation of apomorphine-evoked stereotyped behaviors in subjects rendered supersensitive to the drug by daily injections of haloperidol (HAL) for 3 weeks. The findings suggest that the commonly reported suppressant action of Li on spontaneous behavior is not attributable to overt toxicity or to diminished growth rate. Similarly, these health factors do not account for the ability of chronic Li treatment to suppress the behavioral manifestation of dopaminergic supersensitivity associated with long-term HAL exposure.

Animals↗
PubMed1982

Effects of chronic lithium treatment on dopamine receptors in the rat corpus striatum. II. No effect on denervation or neuroleptic-induced supersensitivity.

The influence of chronic dietary lithium administration was evaluated on dopamine receptor supersensitivity in the rat corpus striatum. Supersensitivity was induced with either unilateral destruction of dopamine-containing fibers in the nigrostriatal pathway or with 3 weeks of treatment with haloperidol (HAL). Both treatments elevated [3H]spiroperidol binding sites, but in neither case was this increase in ligand binding affected by chronic dietary Li (brain levels 0.8 to 1.2 mEq/1 tissue). Our rats receiving 21 daily injections of HAL did show a behavioral supersensitivity to the dopamine agonist, apomorphine, and this effect was attenuated by concurrent treatment with dietary Li (accompanying paper). However, in contrast to previous data, this behavioral attenuation could not be linked to the prevention of increased [3H]spiroperidol binding in the corpus striatum. Furthermore, co-administration of dietary Li to subjects injected with HAL for 3 weeks did not reverse the increased density of [3H]spiroperidol binding sites which developed in the corpus striatum. Neither HAL nor Li treatment altered the affinity of the radioligand for its binding site. In the same animals, neostriatal dopamine-sensitive adenylate cyclase was not affected by either long-term dietary Li or chronic neuroleptic treatment, supporting the view that membrane antagonist and agonist sites differentially adapt to chronic alterations of synaptic input. Taken together, the results are incompatible with the hypothesis that the anti-manic action of Li is related to its ability to prevent dopamine receptor supersensitivity.

Adenylyl Cyclases↗
PubMed1982

Chronic lithium decreases blood pressure in spontaneously hypertensive rats.

The effects of chronic lithium treatment on the blood pressure of spontaneously hypertensive rats were examined. Treated rats were fed a pelleted solid diet containing 1.696 g LiCl (40 mmol) /Kg diet. Control rats received a similar diet lacking the lithium. Rats were fed their respective diet for 21 days at which time intra-arterial blood pressure was recorded while the rats were conscious and freely moving. Lithium treated rats had a decreased systolic (20-30 mmHg) and mean (15-20 mmHg) arterial blood pressure as compared to the control spontaneously hypertensive rats. Heart rate was increased in the lithium treated group.

Animals↗
PubMed1981

Lithium treatment decreases blood pressure in genetically hypertensive rats.

Chronic lithium treatment was examined for effects on the blood pressure of spontaneously hypertensive rats (SHRs). Treated rats were allowed continuous access to a pelleted lithium diet (1.7 g LiCl (40 mmol)/kg diet) for 21 days. Control SHRs were fed a similar diet lacking the lithium. Two groups of control rats were examined. One group had continuous access to control diet (ad lib controls); a second group was pair-fed a daily ration of control diet such that their mean body weight remained similar to the lithium treated group (pair-fed controls). Heart rate, systolic, diastolic and mean arterial blood pressures were recorded on day 21 from freely moving conscious rats. Systolic, diastolic and mean arterial blood pressure was significantly lower (approximately 15 mmHg) in the lithium treated SHRs as compared to either control group; the pair-fed and ad lib controls had similar blood pressures at the end of the treatment periods. Heart rate was increased in the lithium treated animals. All rats gained weight during the 21 days of treatment, although the lithium treated group and the pair-fed control group did not gain weight as much or as rapidly as the control group that had continuous access to control diet. Plasma and brain lithium levels were in the moderate range (0.3--0.4 meq/l) and all rats appeared healthy at the end of the experiment. These results suggest that chronic treatment may have clinically relevant effects on blood pressure.

Animals↗
PubMed1981

In vivo release of enkephalin from the globus pallidus.

Push-pull cannulae were acutely positioned through previously implanted guides in the globus pallidus of unanesthetized freely moving cats and rats. During slow-flow perfusions, enkephalin release was detected in resting conditions and increased more than 3-fold when both 50 mM K+ and 1.8 mM Ca2+ were present in the perfusing medium. Local perfusion with veratrine also enhanced enkephalin release. Furthermore, in vivo, electrical stimulation of the rat caudo-putamen enhanced enkephalin release in the pallidum. This latter finding is consistent with a functional strio-pallidal enkephalin-containing pathway previously postulated by immunohistochemical or lesion experiments.

Animals↗