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Biomedical subjects

K L Rogers

Publications and source records attributed to K L Rogers.

32 records · Page 2Linked to original sources

Glutamate receptor agonists cause efflux of endogenous neuroactive amino acids from cerebellar neurons in culture.

Cultured neurons from rat cerebellum were used to examine the effects of glutamate receptor agonists on the release of endogenous amino acids and adenosine. Kainic acid exposure resulted in the release of glutamate, taurine, GABA and alanine in a dose- and calcium-dependent manner. Stimulation with quisqualic acid resulted in the dose- and calcium-dependent release of GABA. N-Methyl aspartic acid did not elicit the release of any neuroactive amino acids. These findings suggest that N-methyl aspartate receptors are not coupled to transmitter release in these cultures, and that kainate and quisqualate receptors may have different neuronal distributions.

Amino Acids↗

Stimulus-coupled taurine efflux from cerebellar neuronal cultures: on the roles of Ca++ and Na+.

Primary cultures of cerebellar neurons obtained from 7-9-day-old rats and grown 7-9 days in vitro (DIV) were used to study the effects of Na+ and Ca++ on K+-evoked taurine release. These cultures, made up largely of granule neurons (90%) and inhibitory interneurons (5-7%), produced a dose-dependent, depolarization-evoked taurine release that was Ca++-dependent at 40 mM K+, and Ca++-independent at K+ concentrations above 40 mM. The dihydropyridine Ca++ channel agonist BAY K 8644 (1 microM) augmented 30 mM K+-evoked release, while the antagonist nifedipine (5 microM) abolished both the BAY K 8644- and K+-enhanced release. Depolarization with the Na+ channel agonist veratridine (50 microM) stimulated taurine efflux, which was completely blocked by pretreatment with tetrodotoxin (2 microM). However, 50 mM K+-evoked taurine release was not affected by tetrodotoxin pretreatment. Substitution of choline Cl for NaCl partially antagonized 50 mM K+-evoked release, and by itself, the Na+ ionophore monensin (50 microM) stimulated release. These results suggest that both K+-evoked and basal taurine release from primary cerebellar neuronal cultures are sensitive to the levels of both intracellular and extracellular Na+ and Ca++. In contrast to previous findings using cerebellar astrocytes, neuronal L-type Ca++ channels, but not voltage-dependent Na+ channels, also appear to be necessary. The implications of these results on taurine's status as a putative neurotransmitter are discussed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

K+-evoked taurine efflux from cerebellar astrocytes: on the roles of Ca2+ and Na+.

The ionic requirements for K+-evoked efflux of endogenous taurine from primary cerebellar astrocyte cultures were studied. The Ca2+ ionophore A23187 evoked taurine efflux in a dose-dependent fashion with a time-course identical to that of K+-induced efflux. The Ca2+-channel antagonist nifedipine had no effect upon efflux induced by 10 or 50 mM K+. In addition, verapamil did not antagonize 50 mM K+-evoked efflux except at high, non-pharmacological concentrations (greater than 100 microM), and preincubation with 2 microM omega-conotoxin had no effect on 50 mM K+-evoked efflux. Similarly, preincubation with 1 mM ouabain had no effect on the amount of taurine released by K+ stimulation, but did accelerate the onset of efflux by 2-4 min. Although 2 microM tetrodotoxin had no effect on K+-evoked release, replacing Na+ with choline abolished the taurine efflux seen in response to K+ stimulation. Together, these findings suggest that neuronal N- and L-type Ca2+- and voltage-dependent Na+-channels are not involved in the influx of Ca2+ which appears to be necessary for K+-evoked taurine efflux, and that in addition to Ca2+, extracellular Na+ is also required.

Animals↗

Dose-dependent, K+-stimulated efflux of endogenous taurine from primary astrocyte cultures is Ca2+-dependent.

The K+-stimulated efflux of endogenous taurine from primary rat cerebellar astrocyte cultures prepared from 7-9-day-old rats was studied at 16-18 days in vitro using HPLC analysis. Taurine efflux was dose-dependent at K+ concentrations between 10 mM and 80 mM, with an EC50 of approximately 50 mM. Maximum stimulation of efflux above basal levels ranged from 56% at 10 mM K+ (204 pmol/min/mg protein) to 470% at 80 mM K+ (960 pmol/min/mg protein). Removal of Ca2+ from the buffer and the addition of either 1 mM EGTA or 10 mM Mg2+ abolished K+-stimulated efflux. Taurine efflux peaked and fell in parallel with the K+ concentration, but with an approximate lag of 3-5 min. The time course and amount of preloaded [3H]taurine released did not differ significantly from that seen for endogenous efflux. Basal taurine efflux varied inversely with the extracellular concentration of Ca2+ over the concentration range 0-5.0 mM. The observed Ca2+ dependence is consistent with a role for Ca2+ in the regulation of taurine release. Furthermore, taurine release from astrocytes in response to elevated K+ may reflect a neuromodulatory role for this amino acid in the CNS.

Animals↗

HPLC analysis of putative amino acid neurotransmitters released from primary cerebellar cultures.

An HPLC method is described that measures amino acids (putative neurotransmitters and/or neuromodulators) released from primary, dissociated cerebellar cells maintained in monolayer culture. Precolumn derivatization with phenylisothiocyanate, followed by reverse phase chromatography with UV detection was used to quantitate the phenylcarbamyl amino acid derivatives in a chemically defined medium. Quantitation was linear, reproducible and sensitive to one picomole. This method is useful for the measurement of putative neurotransmitters GABA, glutamate, aspartate, taurine and adenosine, and can easily be modified to analyze other amino acids in physiological samples.

Amino Acids↗

Rational use of sedative/hypnotics.

Among medications targeted at the central nervous system, sedative/hypnotics are the most widely prescribed. The use of sedative/hypnotics is reviewed in the context of historical influences on prescribing practice and from a current neuroscience perspective. Recommendations are made regarding appropriate applications for these drugs, and the principles for choosing one drug over another are emphasized.

Anti-Anxiety Agents↗

Biphasic diameter distribution of adipocytes from lean and obese rats.

The present study was conducted to determine if adipocyte diameter distributions of lean and obese Zucker rats were skewed (biphasic) and to quantify the extent to which skewed diameter distributions affect the accuracy of estimating average cell size. Diameter distributions were significantly biphasic for both lean and obese rats. The biphasic nature of the distributions was due to the presence of a large proportion of adipocytes 20-40 microns in diameter (30-60% of cell population). The proportion of these small cells was greater in obese than lean rats. The extent to which average diameter calculated from diameter distribution data underestimated cell size was a function of the extent to which diameter distributions were skewed.

Adipose Tissue↗

Benign X-linked myopathy with acanthocytes (McLeod syndrome). Its relationship to X-linked muscular dystrophy.

Two healthy men with McLeod syndrome, a rare X-linked recessive phenotype characterized by acanthocytosis and weakened red blood cell antigenicity in the Kell blood group system, have been investigated. Both men showed raised blood creatine kinase levels, with myopathic EMG abnormalities. Biopsies of the quadriceps muscle showed the features of an active myopathy although there was no clinical evidence of muscular abnormality. The combination of the association of membrane abnormalities in red blood cells and a myopathy in both McLeod phenotype and Duchenne muscular dystrophy suggests that these syndromes may be due to related genetic abnormalities. The genetic locus for McLeod phenotype is situated near the end of the short arm of the X chromosome. The locus for Duchenne muscular dystrophy is unknown but it has been postulated that it is also situated on the short arm of the X chromosome at Xp 21. The occurrence of a subclinical X-linked myopathy with acanthocytosis (McLeod phenotype) thus raises the possibility of a new approach to genetic investigations in Duchenne muscular dystrophy, and in the related milder forms of this disease.

Acanthocytes↗

The effect of weight loss and weight maintenance on high density lipoprotein cholesterol and selected tissue cholesterol levels in lean and obese Zucker rats.

Obese and lean Zucker rats were studied to compare the effects of a 6-week weight loss regimen (period 1) and a subsequent 4-week weight maintenance period (period 2) on high density lipoprotein (HDL2, d = 1.063-1.125 g/ml) cholesterol, plasma, adipose tissue, liver, and total body cholesterol. The effects of weight loss were compared with animals not subjected to weight reduction (control, period O). Weight loss was achieved by reducing food intake below maintenance levels. Plasma cholesterol did not change significantly among the three periods in obese and lean rats. HDL2 cholesterol was higher (P less than 0.05) in obese and lean rats at period 2 compared with the other periods. Adipose tissue cholesterol (per cell) did not differ among the three periods in obese and lean rats. Liver cholesterol (milligrams/gram liver) decreased significantly (P less than 0.05) at period 1 and sustained this level at period 2 in lean rats, whereas liver cholesterol was unchanged among the three periods in obese rats. Carcass cholesterol (milligrams/gram carcass) in obese rats increased significantly (P less than 0.05) after period 1 and sustained this level after period 2. Carcass cholesterol concentration was unchanged in lean rats. These data suggest that consideration must be given to homeostatic mechanisms of carcass and liver cholesterol concentrations in studies examining changes in plasma HDL2 cholesterol levels.

Adipose Tissue↗

Possible role of glutathione in the antitumor effect of a copper-containing synthetic superoxide dismutase in mice.

The effect of glutathione and a glutathione reductase inhibitor on the antitumor effect of Cu(II)(3,5-diisopropylsalicylate)2 (CuDIPS) was studied. CuDIPS is a low-molecular-weight copper coordination compound that exhibits superoxide dismutase-like activity. CuDIPS had antitumor activity against intraperitoneal Ehrlich ascites carcinoma in Swiss mice. A single ip injection of glutathione partially eliminated the antitumor effect of CuDIPS, whereas a single ip injection of 1,3-bis(2-chloroethyl)-1-nitrosourea enhanced the antitumor effect of CuDIPS. These results are consistent with the hypothesis that CuDIPS exerts part of its antitumor effect by producing H2O2.

Animals↗

Prevalence of antichlamydial antibody in London blood donors.

The prevalence of type-specific antichlamydial antibody in a population of blood donors in London was studied using a microimmunofluorescence test. Twenty-six (17%) of 150 women and 38 (26%) of 150 men had antichlamydial antibody (IgG at greater than or equal to 1/16 or IgM greater than or equal to 1/8 or both). Of these, five (3%) women had one (0.75%) man had this antibody directed against Chlamydia trachomatis serotypes D-K, responsible for genital infections, and one man had antibody to Chlamydia psittaci agents. The remaining 57 men and women had antibody against an atypical chlamydial isolate designated Chlamydia IOL-207, which is iodine-negative and serologically distinct from both C trachomatis and C psittaci. The nature and location of infection by this agent are obscure. The results of this study suggest that the prevalence of sexually transmitted infection with C trachomatis serotypes D-K in a normal adult population in London is very low.

Antibodies, Bacterial↗