PubMed Health⌕ Search

Biomedical subjects

S M Waters

Publications and source records attributed to S M Waters.

11 recordsLinked to original sources
PubMed2001

Immunohistochemical localization of the neuropeptide Y Y1 receptor in rat central nervous system.

The diverse effects of neuropeptide Y (NPY) are mediated through interaction with G-protein coupled receptors. Pharmacological analysis suggests the Y1 receptor mediates several of NPY's central and peripheral actions. We sought to determine the distribution of Y1 protein throughout the rat central nervous system by means of indirect immunofluorescence using the tyramide signal amplification method and a novel, amino terminally-directed Y1 antisera. This antisera was verified as specific for Y1 by solution-phase competition ELISA, Western blot and in situ blocking experiments. High concentrations of Y1 immunoreactivity were found in the claustrum, piriform cortex (superficial layer), arcuate hypothalamic nucleus, interpeduncular nucleus, paratrigeminal nucleus, and lamina II of the spinal trigeminal nucleus and entire spinal cord. Moderate levels of Y1 immunoreactivity were found the in the main olfactory bulb, dorsomedial part of suprachiasmatic nucleus, paraventricular hypothalamic nucleus, ventral nucleus of lateral lemniscus, pontine nuclei, mesencephalic trigeminal nucleus, external cuneate nucleus, area postrema, and nucleus tractus solitarius. Low levels of Y1 immunostaining were distributed widely throughout layers II-III of the cerebral cortex (i.e., orbital, cingulate, frontal, parietal, insular, and temporal regions), nucleus accumbens core, amygdalohippocampal and amygdalopiriform areas, dentate gyrus, CA1 and CA2 fields of hippocampus, principal and oral divisions of the spinal trigeminal nucleus, islands of Calleja and presubiculum. These findings are discussed with reference to previously reported receptor autoradiography, immunohistochemistry and mRNA analyses to further support the role of Y1 in NPY-mediated biology.

Amino Acid Sequence↗
PubMed2000

Distribution of galanin-1, -2 and -3 receptor messenger RNAs in central and peripheral rat tissues.

Galanin is a neuropeptide widely expressed in the central nervous system and periphery. In rat, three galanin-binding receptors have been cloned and characterized. We report the qualitative and quantitative distribution of galanin-1, galanin-2, and galanin-3 messenger RNAs in central and peripheral rat tissues by reverse transcription-polymerase chain reaction and solution hybridization/RNase protection assays, respectively. Galanin-1 messenger RNA was detected exclusively in the central and peripheral nervous system with highest expression in hypothalamus, amygdala, spinal cord and dorsal root ganglia. Galanin-2 messenger RNA was highly expressed in hypothalamus, dorsal root ganglia, and kidney with moderate expression in several other tissues. Galanin-3 messenger RNA was widely distributed at low to moderate levels in many central and peripheral tissues. The observed expression of multiple galanin receptors in several tissues including hypothalamus, anterior pituitary and spinal cord supports earlier pharmacological studies suggesting the presence of more than one receptor subtype in these regions. The presence of multiple galanin receptors in these tissues in conjunction with the detection of a single subtype, galanin-2, in tissues such as heart and intestine, illustrates the potential complexity of galanin-associated actions in rat central nervous system and periphery.

Animals↗
PubMed1997

Alterations of peptide metabolism and neuropeptidase activity in senile dementia of the Alzheimer's type.

Work in our laboratory has shown that in addition to previously characterized changes in the level of neuropeptides in SDAT brain, the activity of degradative enzymes responsible for peptide metabolism is also affected. In addition to other reported alterations in peptide metabolism, we have observed that SS-28 degradation is increased in Brodmann area 22 whereas substance P degradation is increased in temporal cortex. Changes in the degradation of these neuropeptides known to be affected in SDAT correlate well with alterations in the activity of specific neuropeptidases. Trypsin-like serine protease activity is increased in SDAT Brodmann area 22 which parallels the increased degradation of SS-28. The activity of MEP 24.15 is decreased in temporal cortex which corresponds to the decreased degradation of substance P. Changes in the activity of these degradative enzymes in SDAT brain can potentially affect the action of other neuropeptide substrates because the neuropeptidases discussed here terminate the action of several neuropeptides. As more neuropeptide and degradative peptidase alterations are discovered in SDAT, greater emphasis may be placed on the role that peptides and neuropeptidases play in the progression of SDAT.

Aged↗
PubMed1997

Effect of dopaminergic drugs on processing and degradative neuropeptidase mRNA in rat frontal cortex and caudate-putamen.

Drugs which act upon central dopamine receptors alter the level, mRNA expression and in vitro degradation of neuropeptides associated with dopamine neuron regulation. Changes in the degradation of certain neuropeptides are correlated with significant alterations in the activity of specific neuropeptidases, namely aminopeptidase N (APN) and neutral endopeptidase 24.11 (NEP 24.11). In the present study, we sought to examine the molecular mechanism of neuropeptidase activity changes in response to dopaminergic drug treatment. The effects of dopaminergic drugs on the mRNA level of APN and NEP 24.11 were determined by RNase protection assays of RNA extracted from rat frontal cortex and caudate-putamen. Additionally, the effects of dopaminergic drugs on the mRNA expression for the neuropeptide processing enzymes, prohormone convertase 1 (PC1) and PC2, were determined. After 7-day administration of the dopamine receptor antagonist, haloperidol (1 mg/kg), no effect on the mRNA expression of APN, NEP 24.11, PC1 or PC2 was observed in either of the rat brain regions studied. Administration of the dopamine receptor agonist, apomorphine (5 mg/kg, bid), altered only the expression of APN mRNA in rat caudate-putamen, where the greatest effect on APN activity has been previously observed. These results suggest that alterations in other post-transcriptional events, such as mRNA translation or insertion of neuropeptidase protein into the membrane, likely play a larger role than changes in mRNA expression in the modulation of neuropeptidase activity.

Animals↗
PubMed1996

Subchronic haloperidol administration decreases aminopeptidase N activity and [Met5]enkephalin metabolism in rat striatum and cortex.

Previously we have shown that subchronic intraperitoneal (i.p.) administration of haloperidol decreases the degradation of [Met5]enkephalin by regional brain slices (Waters et al., 1995, J. Pharmacol. Exp. Ther. 274, 783). In the present study, subchronic (7-day i.p.) administration of haloperidol (1 mg/kg) decreased the accumulation of aminopeptidase-derived fragments Tyr and Gly-Gly-Phe-Met on cortical and striatal slices. The accumulation of Tyr-Gly-Gly, however, was not altered by haloperidol treatment on slices from either region. Further, aminopeptidase N activity was decreased in P2 membranes isolated from either the cortex or striatum of haloperidol-treated animals. These data suggest that the haloperidol-induced decrease in [Met5]enkephalin metabolism results, at least in part, from a reduction in the activity of aminopeptidase N.

Amino Acid Sequence↗
PubMed1996

Haloperidol and apomorphine differentially affect neuropeptidase activity.

In addition to their well characterized effects at dopamine receptors, neuroleptic drugs have been shown to affect the level and in vitro metabolism of neuropeptides. In the present study, the effect of acute and subchronic administration of the neuroleptic haloperidol and the nonselective, dopamine agonist apomorphine on neuropeptidase activity was determined in regional, rat brain P2 membranes. Subchronic administration of haloperidol decreased the activity of aminopeptidase N in the frontal cortex and caudate-putamen. In contrast, subchronic administration of apomorphine increased aminopeptidase N activity in the frontal cortex and caudate-putamen. Neutral endopeptidase 24.11 also was affected differentially in the caudate-putamen, but both subchronic haloperidol and apomorphine decreased neutral endopeptidase 24.11 activity in the frontal cortex. Metalloendopeptidase 24.15 activity was decreased in the caudate-putamen after acute haloperidol and increased in the frontal cortex after acute apomorphine administration; however, no effect was noted after subchronic administration of either drug. Angiotensin converting enzyme was not affected by any treatment. Therefore, neuroleptic-induced alterations in aminopeptidase N, neutral endopeptidase 24.11 and metalloendopeptidase 24.15 activity may account for previously reported alterations in neuropeptide degradation. In view of the interaction between mesocorticolimbic dopamine neurons and neuropeptides, e.g., substance P, neurotensin and enkephalins, neuroleptic-induced alterations in the activities of neuropeptidases, and thus neuropeptide metabolism can, in turn, play a role in modulating midbrain dopaminergic activity.

Animals↗
PubMed1995

Alterations of substance P metabolism and neuropeptidases in Alzheimer's disease.

The levels of specific neuropeptides and the activity of neuropeptidases known to degrade neuropeptides have been shown to be altered in senile dementia of the Alzheimer's type (SDAT) postmortem brain. We examined the metabolism of exogenous substance P, a neuropeptide with a putative role in SDAT pathology, in human postmortem temporal cortex, hippocampus, and caudate membrane homogenates from SDAT and sex- and age-matched control brain. The activity of two neuropeptidases known to metabolize substance P, neutral endopeptidase E.C.3.4.24.11 and metalloendopeptidase E.C.3.4.24.15, was also determined in the same postmortem, human tissue samples. The metabolic half-life of substance P was significantly increased in SDAT, postmortem, temporal cortex. The increased half-life of substance P was correlated with a decreased activity of the metabolic enzyme metalloendopeptidase 24.15 in temporal cortex. Substance P metabolism was not significantly altered in hippocampus or caudate tissues from SDAT brain compared to controls. The alteration of neuropeptidases demonstrated in this study and as shown by altered substance P metabolism may have a significant effect on the level of several biologically important neuropeptides in SDAT brain.

Aged↗
PubMed1995

Neuropeptide metabolism on intact, regional brain slices: effect of dopaminergic agents on substance P, cholecystokinin and Met-enkephalin degradation.

Neuroleptic drugs have been shown to affect the level and messenger ribonucleic acid of specific neuropeptides. The effect of subchronically administered neuroleptics on neuropeptide metabolism, however, has not been systematically characterized. In the present study, the effect of neuroleptics and other dopaminergic compounds on substance P (SP), cholecystokinin and met-enkephalin degradation was determined on intact, regional, rat brain slices. After 7-day administration of haloperidol (1 mg/kg) or chlorpromazine (20 mg/kg), SP degradation was decreased in caudate-putamen and nucleus accumbens. After administration of the dopaminergic agonist apomorphine (5 mg/kg, b.i.d.), SP degradation was increased in the nucleus accumbens. The dopamine D2-receptor antagonist sulpiride (100 mg/kg, b.i.d.) produced no effect on SP degradation. Met-enkephalin degradation was decreased after haloperidol administration in both frontal cortex and caudate-putamen and unaffected by apomorphine administration. The metabolism of cholecystokinin was not affected by neuroleptic treatment. Studies performed with specific peptidase inhibitors suggested that neutral endopeptidase 24.11, metalloendopeptidase 24.15 and aminopeptidases degrade SP on caudate-putamen and nucleus accumbens slices. Therefore, alterations in these peptidases may be responsible for the change noted in SP degradation after dopaminergic compound administration. These metabolic changes noted after neuroleptic administration may therefore contribute to neuroleptic-induced alterations in regional peptide levels.

Animals↗
PubMed1994

Acute administration of neuroleptics decreases neurotensin metabolism on intact, regional rat brain slices.

Treatment with antipsychotic agents has been shown to affect both neurotensin (NT) levels and the activities of enzymes implicated in the metabolism of NT. In the present study the effects of i.p. administered antipsychotics and dopaminergic agents on NT metabolism were examined in the microslice preparation from discrete regions of rat brain. Significant degradation of NT 1-13 with the concomitant production of NT fragments, including NT 1-8, 1-10, 1-11 and 9-13, occurred after incubating for 2 hr regionally dissected microslices with 100 microM NT 1-13. Acute administration (i.p.) of haloperidol (3 mg/kg) 1 hr before slice preparation had no effect on NT metabolism in any of the regions studied. Acute administration of either haloperidol (3 mg/kg) or chlorpromazine (20 mg/kg) 24 hr before slice preparation decreased NT metabolism significantly, as indicated by decreases in both NT degradation and formation of NT 1-8 in both the nucleus accumbens and caudate-putamen. Furthermore, a decrease in the formation of biologically active NT 9-13 was detected in the nucleus accumbens after neuroleptic administration 24 hr before slice preparation. Assay of crude membrane homogenates revealed a significant reduction in the NT-degrading enzyme metalloendopeptidase 24.15 (E.C. 3.4.24.15) activity in the caudate-putamen of haloperidol-treated rats. The level of NT metabolism remained significantly reduced at 48 hr after haloperidol administration, but returned to that of the control level by 96 hr. Acute administration of apomorphine (2 i.p. injections of 20 mg/kg) increased NT degradation on slices from the nucleus accumbens, but not on slices from the caudate-putamen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Low-dose insulin infusion in the treatment of diabetic ketoacidosis: bolus versus no bolus.

The effects of an initial iv bolus of insulin upon plasma glucose, blood gases, and electrolytes were assessed in 19 children with 20 episodes of diabetic ketoacidosis treated by a continuous low-dose insulin infusion of 0.1 unit/kg/hour. An iv bolus of insulin administered prior to low-dose insulin infusion accelerated the decline of plasma glucose concentration during the first hour of treatment, but differences in decline of mean plasma glucose concentration were not apparent thereafter. The mean time required for attaining "normoglycemia" (250 mg/dl) was similar, whether or not the initial bolus of insulin was given, with a smooth and predictable correction of initial hyperglycemia in the majority of children. However, an accelerated response was more frequent in those patients with compensated metabolic acidosis, who received an initial iv bolus of insulin; those with more severe metabolic acidosis took longer to recover. The data suggest that an initial iv bolus of insulin may not be required nor desirable in the majority of children with diabetic ketoacidosis treated by a standard low-dose insulin infusion regimen.

Adolescent↗