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C K Atterwill

Publications and source records attributed to C K Atterwill.

At least 55 records · Page 3Linked to original sources
PubMed1984

Effects of thyroid status on clonidine-induced hypoactivity responses in the developing rat.

Clonidine-induced hypoactivity was studied in rats made neonatally hypo- and hyperthyroid (PTU or T4 administered between 1-27 days postnatally) as an indication of central presynaptic alpha 2-adrenoceptor function. Paradoxically, at 28 days postnatally both treatments caused an increase in clonidine-hypoactivity compared with untreated control animals, which was not due to sex differences amongst littermates in the various groups. It is proposed that whereas the hyperthyroid neonate data perhaps reflect an enhancement of presynaptic alpha 2 function similar to that seen in the adult rat brain, the result obtained for the hypothyroid neonates could perhaps be due to a retardation of the ontogeny of central noradrenergic neurones.

Animals↗
PubMed1984

Effects of thyroid status on presynaptic alpha 2-adrenoceptor function and beta-adrenoceptor binding in the rat brain.

The effect of thyroid status on noradrenergic synaptic function in the mature rat brain was examined by measuring presynaptic alpha 2- and post-synaptic beta-adrenoceptors. Repeated triiodothyronine (T3) administration to rats (100 micrograms/kg X 14 days: hyperthyroid) caused an 18% increase in striatal beta-adrenoceptors as shown by [3H]-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU X 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic beta-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic alpha 2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic alpha 2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic alpha 2-adrenoceptor function. These results show firstly that changes in thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and post-synaptic adrenoceptor function. Secondly, there appear to be T3-induced changes in beta-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.

Animals↗
PubMed1984

Characterization of Na+,K+-ATPase in cultured and separated neuronal and glial cells from rat cerebellum.

The activities of certain properties of sodium, potassium-activated adenosine triphosphatase (Na+,K+-ATPase; EC 3.6.1.3) were examined in cultures and perikarya fractions enriched in rat cerebellar nerve cells or astrocytes, in comparison with preparations from whole immature and adult rat cerebellum and derived synaptosomal fractions, as well as nonneural tissue such as the kidney. The specific activity of Na+,K+-ATPase was markedly higher in the freshly isolated astrocytes than in the nerve cells (3-15-fold greater depending on neuronal cell type). In contrast, the specific activity of the enzyme was about twice as high in the primary neuronal as in the astrocytic cultures after 14 days in vitro. In membrane preparations from the whole cerebellum, synaptosomal fractions, and total perikarya suspensions the inhibition of enzyme activity by ouabain indicated complex kinetics, which were consistent with the presence of two forms of the Na+,K+-ATPase (apparent Ki values of about 10(-7) M and 10(-4)-10(-5) M, respectively), the high-affinity form accounting for 60-75% of the total activity. The interaction of the enzyme with ouabain was apparently similar in perikarya preparations of granule neurones, Purkinje cells, and astrocytes. Differences were, however, observed in the properties of the Na+,K+-ATPase of cultured neurones and astrocytes. The latter contained predominantly, but not exclusively, an Na+,K+-ATPase with low affinity for ouabain (73% of the total) that is similar to the single enzyme form in the kidney. This form constituted a significantly smaller proportion of the Na+,K+-ATPase in the cultured neuronal preparations (55%). It would appear, therefore, that in membrane fractions from preparations enriched in different separated and cultured neural cell types both the high- and the low-affinity forms of the enzyme, in terms of interaction with ouabain, are expressed. Depending on the class of cells these enzyme forms constituted a different proportion of the total activity, but both forms seemed to be present in every type of cell examined, even after taking into account the contribution in the enriched preparations of the contaminating cell types. In contrast with the results on the Na+,K+-ATPase activity determined under optimal conditions in preparations derived from disrupted cells, differences could not be detected between the cultured cell types when the effect of ouabain on the uptake of 86Rb into "live cells" was estimated as a measure of in situ ion pump activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗
PubMed1984

Development of markers for cholinergic neurones in re-aggregate cultures of foetal rat whole brain in serum-containing and serum-free media: effects of triiodothyronine (T3).

Development has been studied in re-aggregate cultures derived from the 16 day foetal rat brain and the effects of triiodothyronine (T3) investigated. Cultures were maintained in either a medium containing 10% serum (S+), or in serum-free culture medium (S-) or in serum-free medium containing 30nM T3. The muscarinic cholinoceptor, measured by specific binding of [3H]-quinuclidinyl benzitate ([3H]-QNB) at 9 and 14 days in vitro, was at a lower level in the serum-free cultured cells compared with those in serum-containing culture medium (S+). In cultures in the latter medium, receptor concentration at day 14 was of a similar magnitude to that in rat brain at an equivalent postnatal age. Binding increased with development from 9 to 14 days in vitro in the S+ medium but not in the S- medium. T3 treatment caused an 85% increase in [3H]-QNB binding compared with the cultures in S- medium at day 14 to a level equivalent to that found in the cells grown in S+ medium. This increase was reflected in the Bmax but not in the KD (approx. 0.1nM). Choline acetyltransferase (ChAT) activity developed more slowly in the S- medium than in the S+ medium where the specific activity approximated values obtained in vivo. T3 treatment of cultures grow in S- medium significantly enhanced the developmental rate of increase of ChAT activity. The characteristics of [3H]-choline uptake and metabolism in the cultures was examined. Uptake was strictly Na+-independent but was energy-dependent, and inhibited by 2, 4'-dinitrophenol (2, 4'-DNP) and cooling (0-4 degrees C). Neither iodoacetate nor ouabain had any effect on the amount of uptake. Hemicholinium (HC3) was a potent inhibitor of uptake (70% inhibition at 10 microM HC3). Metabolism studies showed virtually no conversion to [3H]-acetylcholine ([3H]-ACH) in reaggregates grown in either the S+, S- or T3 containing media. However, a small amount of [3H]-choline was incorporated into phosphorylcholine. T3 treatment had no effect on this metabolic profile. The kinetics of [3H]-choline uptake by the re-aggregates was also studied in the re-aggregate cultures (after 12 and 22 days in vitro) using [3H]-choline at 0.05-100 microM. Both Eadie-Hofstee transformation and least-squares analysis of the data showed that the uptake comprised only a single low-affinity component with an apparent Kt = approx. 50 microM. Unlike ChAT and [3H]-QNB binding, there appeared to be no difference between the uptake in the different culture conditions. 6 It is concluded that the differentiation of cholinergic neurones and muscarinic receptors in serum-free cultured re-aggregates from foetal rat brain is enhanced by thyroid hormone treatment. The development of [3H]-choline uptake does not seem to be associated with cholinergic cells under these culture conditions, and is unaffected by thyroid hormone treatment.

Animals↗
PubMed1982

Repeated administration of triiodothyronine (T3) to rats enhances nigrostriatal and mesolimbic dopaminergic behavioural responses.

A once daily injection to rats of triiodothyronine (T3; 100 micrograms/kg s.c.) for 10 days enhanced the locomotor responses of rats pretreated with tranylcypromine (5 mg/kg) to an injection into the nucleus accumbens of dopamine (5 micrograms bilaterally), when tested 24 hr after the last T3 administration. This treatment did not, however, alter the control responses of tranylcypromine-pretreated rats to injection of saline (1 microliter bilaterally). Injection of T3 for 10 days enhanced the circling responses of unilateral nigrostriatal-lesioned rats to apomorphine (0.5 mg/kg) but not to methamphetamine (0.5 mg/kg). The probable explanation for the latter result was the finding that repeated T3 administration lowered basal striatal dopamine concentrations. The treatment also produced a trend towards reduced dopamine concentrations in the n. accumbens, although the difference did not reach statistical significance. These data suggest that repeated T3 injection causes an increased post-synaptic function of both the nigrostriatal and mesolimbic dopamine systems in rat brain.

Animals↗
PubMed1982

Effects of repeated lithium administration on the subcellular distribution of 5-hydroxytryptamine in rat brain.

1 The content and distribution of 5-hydroxytryptamine (5-HT) between subcellular fractions from rat whole brain (excluding cerebellum) were examined following repeated lithium administration. 2 Lithium chloride (3 mEq/kg body wt. s.c.) administered twice daily for 3 days produced no change in the 5-HT content of primary subcellular fractions (P1-nuclear; P2-crude synaptosomal; SNT-soluble) measured on the 4th day. 3 Similarly, repeated lithium treatment alone did not appear to produce increases in the 5-HT content of either cytoplasmic (S) or vesicular (M2) fractions derived from hypo-osmotically disrupted synaptosomes (P2) when compared to control rats receiving NaCl only. 4 One hour after monoamine oxidase inhibition with tranylcypromine, there was a further selective 25% increase in 5-HT accumulation in the lithium-treated rats over control values in the soluble cytoplasmic fraction (S) and in fractions containing occluded cytoplasm only. This increase did not occur in the synaptic vesicle fraction (M2). This corresponds to an increase in 5-HT turnover rate due to the lithium treatment of approx. 50%. 5 These findings lend additional support to the hypothesis that lithium treatment alters the intraneuronal storage or compartmentation of 5-HT between vesicles and cytoplasm.

Animals↗
PubMed1980

Lack of effect of repeated electroconvulsive shock on [3H]spiroperidol and [2H]5-hydroxytryptamine binding and cholinergic parameters in rat brain.

Repeated electroconvulsive shock (ECS) administered on alternate days for 10 days produced no changes in rat striatal [3H]spiroperidol binding measured 24 h after the last shock compared to anaesthetised controls. Similarly, there was no change in while brain specific [3H]5-HT binding. Sodium-dependent high affinity [3H]choline uptake (HAUC) and ChAT were also unaltered in striatal and hippocampal samples following repeated ECS. Acute administration of Pentylenetetrazol did produce an increase in hippocampal HAUC immediately postictally. However, ECS (Xl) did not change HAUC measured 1 h postictally. An effect of halothane on HAUC was noted in these experiments indicating the importance of an evaluation of anaesthetic effects in ECS studies.

Animals↗