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Biomedical subjects

M Nielsen

Publications and source records attributed to M Nielsen.

At least 235 records · Page 13Linked to original sources
PubMed1986

Repeated treatment with clenbuterol produces desensitization of rat brain beta- and alpha 2-adrenoceptors without changes of alpha 1-adrenoceptors.

The effects of single and repeated administrations of the beta-agonist, clenbuterol (0.5 mg/kg i.p., twice daily for 4 or 7 days) were measured in the open-field test as responsiveness of rats to beta- (clenbuterol), alpha 2-(clonidine) and alpha 1-(phenylephrine) adrenergic stimulation. Furthermore, the effects of such treatment on beta- and beta 1-adrenoceptor binding in the rat brain cortex were studied. Repeated administration of clenbuterol failed to change the exploratory activity, in contrast to the acute sedative effect. Repeated treatment with clenbuterol resulted in a decrease in [3H]dihydroalprenolol binding to cortical beta-adrenoceptors. A single dose of clenbuterol reduced the clonidine-induced sedation and repeated treatment of clenbuterol abolished this sedation. Clenbuterol did not affect the action of phenylephrine nor did it change the binding of [3H]prazosin. These results indicate that repeated administration of a beta-agonist produces a rapid appearance of beta- and alpha 2-adrenoceptor subsensitivity, which it not followed by alpha 1-adrenoceptor changes.

Animals↗
PubMed1986

Granular cell tumor of the uvula.

We describe the first case of granular cell tumor (GCT) of the uvula, which occurred in an 18-year-old woman. GCT is a relatively rare tumor, and is almost always benign. The most frequent locations are the skin and the oral cavity. These tumors usually present clinically as small, slowly growing tumors of characteristic histological appearance. Although its histogenesis is uncertain, our study as well as recent reports support a currently held theory of a neurogenic derivation. The recommended treatment for the granular cell tumor is local excision whenever possible.

Adolescent↗
PubMed1986

Differentiation of Cl-/Ca2+-dependent and sodium dependent 3H-glutamate binding to cortical membranes from rat brain by high energy radiation inactivation analysis.

The molecular weights of 3H-L-glutamate binding in the presence of chloride and calcium ions and in the presence of sodium ions were determined by the high energy irradiation technique. The molecular weight of sodium dependent 3H-L-glutamate binding, which has pharmacological specificities similar to the high-affinity uptake system for L-glutamate, was 670,000 daltons. The high-energy radiation inactivation study of chloride and calcium dependent and sodium independent 3H-L-glutamate binding is consonant with the idea that, this binding represent glutamate transport into resealed plasma membrane vesicles.

Animals↗
PubMed1986

Glycine antagonists structurally related to 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol inhibit binding of [3H]strychnine to rat brain membranes.

[3H]Strychnine binding to rat pons + medulla membranes was used as a measure of glycine receptors or glycine receptor-coupled chloride channels in vitro. A series of compounds structurally related to 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), which previously were shown to antagonize glycine responses in cat spinal cord, inhibited [3H]strychnine binding in micromolar concentrations. The most potent of these glycine antagonists, 5,6,7,8-tetrahydro-4H-isoxazolo[3,4-d]azepin-3-ol (iso-THAZ), was also the most potent inhibitor of [3H]strychnine binding, with a Ki of 1,400 nM. The Ki value for strychnine was 7.0 nM, whereas the Ki value for the mixed gamma-aminobutyric acid (GABA)/glycine antagonist 3 alpha-hydroxy-16-imino-5 beta-17-aza-androstan-11-one (RU 5135) was only 4.6 nM. Sodium chloride (1,000 mM) enhanced the affinity of strychnine, brucine, isostrychnine, and the nonselective GABA antagonist pitrazepin for [3H]strychnine binding sites, whereas the affinities of glycine, beta-alanine, and taurine were reduced. These sodium chloride shifts, however, were not predictive of antagonist or agonist properties, since the sodium chloride shift for the glycine antagonist iso-THAZ and of the other THIP-related antagonists were similar to those of the glycine-like agonists. The various sodium chloride shifts show that different groups of ligands bind to glycine receptor sites in different ways.

Animals↗
PubMed1986

Electrophysiological properties of calcitonin-secreting cells derived from human medullary thyroid carcinoma.

Primary cultures of human medullary thyroid carcinoma tissue were prepared from lymph node metastases in two patients. The parenchymal, cultured cells displayed positive immunocytochemical staining for CT, and the cells also released the hormone into the culture medium. The membrane potential and resistance of the CT-producing cells were 50.1 +/- 8.9 mV and 634 +/- 154 M omega (mean +/- SD, n = 46). TTX sensitive action potentials with maximum rate of rise up to 51 V s-1 were evoked by current injection in Na+-containing solution, whereas TTX insensitive action potentials with maximum rate of rise up to 9 V s-1 were generated in Na+-free solution. These action potentials were reversibly blocked by D-600. We conclude that the action potentials of the human MTC cells have both a Na+ and a Ca2+ component. Ejection of CA2+-free solution close to the cells caused membrane hyperpolarization associated with decreased membrane resistance. The reversal potential of this response was -66.2 +/- 10.9 mV (n = 10), indicating that a permeability increase to Cl- and/or K+ may be involved. We suggest that elevated plasma Ca2+ concentration in vivo may cause increased excitability due to membrane depolarization and resistance increase, thus leading to enhanced Ca2+ influx and hormone secretion.

Action Potentials↗
PubMed1986

Cystosarcoma phyllodes. A review of 19 cases with emphasis on the occurrence of associated breast carcinoma.

The clinico-pathological aspects of 19 cases of cystosarcoma phyllodes (CP) were reviewed with special attention to the occurrence of associated breast carcinoma (BC). Twelve women had histologically benign, 4 had borderline and 3 malignant CP. Recurrent CP was diagnosed in 9 women within 1 to 15 years after initial treatment. Of the 19 women, 5 had associated in situ or invasive BC, 2 with the primary CP and 3 with its recurrences. In 1 case the BC was located within the confines of the CP, whereas in 4 women the CP and BC were separate lesions. The frequency of incidentally found BC in this group of women with CP does not support the hypothesis of an increased risk of BC development in women with CP.

Breast↗
PubMed1985

Interaction of pitrazepin with the GABA/benzodiazepine receptor complex and with glycine receptors.

Pitrazepin (3-(piperazinyl-1)-9H-dibenz(c,f)triazolo(4,5-a)azepin) is a new GABAA receptor antagonist reported to antagonize electrophysiological effects of GABA. We have investigated in some detail the interaction of pitrazepin with the GABA/benzodiazepine receptor chloride channel complex. Pitrazepin was found to be a competitive inhibitor of the GABAA receptor which is coupled to [3H]diazepam and [35S]TBPS binding sites; the KI value obtained by Schild analyses was 80 nM. Although pitrazepin interacted weakly with BZ receptors the compound did not affect the chloride gating mechanism (labelled with [35S]TBPS or [3H]avermectin B1a). Further, pitrazepin was a non-selective GABA antagonist since glycine receptors, labelled with [3H]strychnine, were affected at low concentrations (the KI values in rat brain-stem were 71-110 nM).

Animals↗
PubMed1985

Molecular size of [3H]WB-4101-binding sites in rat cortex as determined by radiation inactivation.

The molecular weight of the [3H]WB-4101-binding sites in rat cerebral cortex was estimated by the irradiation-inactivation technique. The molecular weight was found to be dependent on the assay concentrations of the radioligand in the binding assay. Assays with a [3H]WB-4101 concentration of 0.25 nM showed a molecular weight of 62,100 daltons and 5.1 nM showed 50,800 daltons. Scatchard transformation of the [3H]WB-4101-binding data shows two binding sites (high-affinity: KD = 0.09 nM, Bmax = 9.1 pmoles/g; low-affinity: KD = 20 nM, Bmax = 80 pmoles/g). It is suggested that the two binding exist at two distinct molecules and in that case the observed molecular weights of 62,100 and 50,800 daltons are not true values because the determinations are carried out on a mixture of the two molecule populations. The distribution of the two binding sites was calculated for the two radioligand concentrations, 0.25 nM and 5.1 nM; and on this background the "true" molecular weights of the two [3H]WB-4101-binding sites were estimated to be 68,300 daltons for the high-affinity molecule and 41,400 daltons for the low-affinity molecule. Competition studies with a variety of adrenergic agonists and antagonists against [3H]WB-4101 supported the hypothesis that only the high-affinity binding site is an alpha-1-adrenoceptor.

Animals↗
PubMed1985

Radiation inactivation of brain [35S]t-butylbicyclophosphorothionate binding sites reveals complicated molecular arrangements of the GABA/benzodiazepine receptor chloride channel complex.

[35S]t-Butylbicyclophosphorothionate ([35S]TBPS), a bicyclic cage convulsant, binds to the anion gating mechanism of the GABA/benzodiazepine receptor chloride channel complex. Using a carefully calibrated radiation inactivation technique, the molecular weight of [35S]TBPS binding complexes from frozen rat cerebral cortex was estimated to be 137,000 daltons. The GABA agonist muscimol reduced [35S]TBPS binding to 0-10% of the control value, in a way which is independent of the radiation dose. This shows that the GABA receptor (Mw = 55,000 daltons) is included in the 137,000-dalton [35S]-TBPS binding complex; the [35S]TBPS binding protein alone accounts for 137,000-55,000 = 82,000 daltons. The pyrazolopyridazine etazolate (SQ 20.009) and etomidate in appropriate concentrations both reduced specific binding of [35S]TBPS. The ability of SQ 20.009 and etomidate to reduce [35S]TBPS binding was greatly reduced by exposure to low radiation doses, suggesting that SQ 20.009 and etomidate reduce [35S]TBPS binding by an allosteric mechanism requiring a molecular structure of 450,000-500,000 daltons. Benzodiazepine agonists (ethyl 4-methoxymethyl-6-benzyloxy-beta-carboline-3-carboxylate, ZK 93423) and inverse agonists (methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, DMCM) enhance and reduce [35S]TBPS binding, respectively, in repeatedly frozen and washed membrane preparations. The effects of ZK 93423 and DMCM on [35S]TBPS binding disappeared upon exposure of membranes to low radiation doses. This suggests that the benzodiazepine receptor site interacts allosterically with the [35S]TBPS binding site, requiring a molecular complex of at least c. 400,000 daltons. The [35S]TBPS site alone in these latter conditions of membrane preparation (repeatedly frozen/washed) revealed a molecular weight of 221,000 daltons (TBPS-site + GABA receptor + unknown structures). The number of binding sites for [35S]TBPS (145 pmol/g tissue) was only slightly higher than for [3H]flunitrazepam (130 pmol/g tissue) in cerebral cortex. These results are all consonant with the conclusion that the GABA/BZ receptor chloride channel complex is composed of highly integrated multimeric subunits, tentatively accounted for by a tetramic complex of molecular weight 548,000 daltons.

Animals↗
PubMed1985

Target sizes of human erythrocyte membrane Ca2+-ATPase and Mg2+-ATPase activities in the presence and absence of calmodulin.

We have investigated the subunit structure of Ca2+-transport ATPase in human erythrocyte membranes using radiation inactivation analysis. All inactivation data were linear on a semilog plot down to at least 20% of the control activity. We found a target size for the calmodulin-dependent Ca2+-ATPase activity of 331 kDa, consistent with the presence of this enzyme as a dimer in calmodulin-depleted ghosts. Membranes which had been saturated with calmodulin before irradiation yield a a similar size of 317 kDa, implying that activation of Ca2+-transport ATPase by calmodulin does not involve significant change in oligomeric structure. Basal (calmodulin-independent) Ca2+-ATPase activity corresponded to a size of 290 kDa, suggesting that this activity resides in the same, or similar-sized, complex as the calmodulin-dependent activity. Mg2+-ATPase activity, however, was found to reside in a smaller complex of 224 kDa, which proved to be statistically distinct from the target size of Ca2+-ATPase activity. It would appear that Mg2+-ATPase is a distinct entity whose function is likely unrelated to the Ca2+-transport ATPase.

Adenosine Triphosphatases↗
PubMed1985

Complex structure of quisqualate-sensitive glutamate receptors in rat cortex.

Multiplicity of excitatory amino acid receptors has previously been demonstrated. The functional size of the quisqualate-type receptors was investigated by high energy radiation inactivation analysis of the binding of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) to rat cortical membranes. The AMPA binding site is coupled to a high molecular weight modulatory unit, which down-regulates the affinity of the binding site for quisqualate, glutamate and AMPA. The estimated molecular target size of the AMPA binding site is different from the reported molecular weight of the glutamate binding site isolated from bovine brain. Furthermore, enhanced [3H]AMPA binding induced by chaotropic ions seems not to be a consequence of removal of the modulatory unit.

Animals↗
PubMed1985

Discriminative stimulus properties of methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), an inverse agonist at benzodiazepine receptors.

Rats (N = 8) were trained to discriminate the stimulus properties of the potent benzodiazepine (BZ) receptor inverse agonist methyl 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) from saline in a two-lever operant task. The initial training dose of DMCM was 0.4 mg/kg at which the discrimination developed slowly; increasing the dose to 0.8 mg/kg resulted in rapid acquisition. However, since convulsions eventually developed during further training (sensitization), the training dose was finally individualized below the convulsive threshold (0.4-0.7 mg/kg). The DMCM cue was mimicked by FG 7142 (10 mg/kg), a non-convulsant anxiogenic beta-carboline, by pentylenetrazol (20-30 mg/kg), and by the GABA antagonist bicuculline (2 mg/kg). The DMCM cue was not, or marginally, blocked by diazepam (2.5 mg/kg) or pentobarbital (10-15 mg/kg). Furthermore, the BZ receptor antagonists CGS 8216 (2.5 mg/kg), ZK 93426 (20 mg/kg), and Ro 15-1788 (20-80 mg/kg) also did not, or only marginally, block the DMCM cue. However, the receptor antagonists (alone) substituted for DMCM although Ro 15-1788 was less effective. The partial BZ receptor agonist ZK 91296 (25 mg/kg), which is structurally similar to DMCM, blocked completely the DMCM stimulus effect. THIP (4 mg/kg) did not block the DMCM cue. To explain these results, we suggest that the repeated DMCM treatment, necessary for maintaining the discrimination, shifts the balancing point ("set-point") for positive (i.e., BZ-like) agonist efficacy versus inverse agonist efficacy, towards inverse action. This hypothesis was supported by the finding of an enhanced ability of GABA to reduce 3H-DMCM binding to cortical neuronal membranes of animals treated chronically with DMCM in a regimen similar to that used to maintain the DMCM discrimination. Furthermore, this treatment did not affect baseline 3H-DMCM binding, baseline or GABA stimulated 3H-diazepam binding, or 35S-TBPS binding (to chloride channels).

Animals↗