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Notes: Summary Dopaminergic binding sites were studied in slices from rat striatum incubated in a physiological medium and using the two highly selective ligands 3H-apomorphine and 3H-domperidone. The clearly biphasic or stretched inhibition of the specific binding of these two ligands by domperidone or apomorphine, respectively allowed to define three distinct classes of binding site. It was demonstrated, by comparing the binding of the 3H-ligand added at the beginning of slice incubation or just before homogenisation of tissue and filtration, that the “specific” bindings only occurred during the incubation of slices. The inhibition constants (K i values) of dopaminergic agents for the three classes of binding site as also the dissociation constants (K d values) of 3H-ligands and the maximal capacity (B max) of the three classes of binding site were closely similar to those of binding sites previously demonstrated on rat striatal membranes, namely D-2, D-3 and D-4 sites (Sokoloff et al. 1980a, b). Their identification on a preparation in which the cellular organisation is largely preserved rules out the possibility that these sites represent an artifact due to membrane preparation. Unexpectedly the addition of guanyl nucleotides like GTP or GppNHp to the slice preparation decreased the binding of 3H-apomorphine to the high affinity sites (particularly to the D-2 sites) while D-4 site binding was correspondingly increased. The guanylnucleotide effect apparently took place before cell disruption and occurred at concentrations similar to those required in striatal membrane preparations. These observations, together with those indicating the presence of high affinity binding sites for dopaminergic agonists in intact striatal cells, suggest that a putative nucleotide regulatory unit of dopamine receptors, is not fully occupied by intracellular GTP but could be interacted with from the external face of the cell membrane.

Notes: Summary In order to document the hypothesis that anti-psychotics may interact with more than one class of cerebral dopamine receptors, the relative potencies of a series of compounds were compared in three behavioral tests and in binding studies with two radioligands. Apomorphine (0.6 mg/kg) simultaneously clicited in rat two kinds of facial stereotypies (sniffing and licking) and a stereotyped climbing behavior, allowing to compare in the same animals the relative potencies of various antipsychotics against the three behaviors. Only some substituted benzamides (Sulpiride, LUR 2366 and DAN 2163) antagonised at significantly lower dosages climbing than sniffing (or licking). The possibility that this discriminant potency might be related to a distinct affinity for two classes of dopamine receptors was investigated by binding studies on striatal membranes with 3H-apomorphine and 3H-domperidone. From lesion and subcellular fractionation studies, two classes of binding sites both labeled with 3H-domperidone but distinguished by apomorphine i.e. D-2 sites with nM affinity and D-4 sites with μM affinity for the dopamine agonist (according to the nomenclature of Sokoloff et al. 1980b) appear to be differently localised in striatum. Thus D-2 sites, whose number decreases after kainate lesion, are not significantly modified following cortical lesions and preferentially sediment with heavy primary subcellular fractions. In contrast D-4 sites, less affected by kainate lesions, are significantly decreased following cortical lesions (−30%) and preferentially sediment with the light subcellular fractions. In addition the apparently heterogenous recognition of total 3H-domperidone binding sites (i.e. the sum of D-2 and D-4 sites) by dopamine and apomorphine persists in the presence of guanosine-5′-triphosphate (pseudo-Hill coefficient of 0.60 instead of 0.55). This suggests that D-2 and D-4 sites cannot be considered as two discrete states of the same receptor strictly convertible one into the other by guanylnucleotides. Whereas most dopamine antagonists inhibited D-2 and D-4 site binding with similar affinities, the three benzamide derivatives with the largest selectivity in behavioral tests displayed 2–3-fold higher affinity for D-4 than for D-2 sites and the ratios of ID50 values of the whole series of antagonists against sniffing (or licking) and climbing behaviors were correlated (P〈0.01) with the ratios of K i values regarding D-2 and D-4 site binding. Also, sulpiride and LUR 2366 unlike haloperidol and metoclopramide, inhibited the total specific 3H-domperidone binding in a biphasic manner. However, the distinction by sulpiride and LUR 2366 of low and high affinity sites did not superimpose that of D-2 and D-4 sites, as distinguished by agonists. In this test the relative proportion of low affinity sites was 2-fold higher than that of D-2 sites and K i values for high affinity sites were lower than that for D-4 sites. Also the heterogeneity of 3H-domperidone sites regarding affinity of LUR 2366 persisted in the presence of low concentrations of apomorphine. Hence low affinity sites for discriminant benzamide derivatives may exist in two forms, distinguished by agonists and possibly interconvertible by GTP. Thus the hypothesis that two classes of central dopamine receptor can be distinguished by some substituted benzamides, but perhaps display no great difference in affinity of agonists in their physiological state, fits partic-ularly well with behavioral data.

Notes: A class of dynamic model approximation techniques based on a frequency domain Taylor series expansion is presented. These methods yield low-order models and are analytical rather than computational in nature; that is, one can retain important parameters (which may be time varying) from the original model in functional form in the low-order model. This feature is very attractive for on-line updating of the simplified model and subsequent control of the process. An example for a tenth-order original model has shown that the analytical low-order models provide excellent approximations to the step response of the original system.

Notes: A new tracer technique is reported for the determination of liquid-solid contacting efficiency and liquid holdup in trickle beds packed with small alumina particles. Holdup was a function of liquid mass velocity for both porous and nonporous packing. Contacting efficiency remained uniform at a level of 65%.

Notes: A type of tandem mass spectrometric scan is described in which m1 +, m2 + and m3, defined in terms of the process m1 + → m2 + + m3, are all varied while maintaining some prescribed relationship between them. The scan can be viewed as a variant upon the neutral loss scan in which the constant mass difference between parent and daughter ion masses is replaced by some other functional relationship. Specific examples of this scan are provided in two simple applications: (i) symmetrical proton-bound dimers are recognized using the functional scan m2 = (m1 + 1)/2; and (ii) symmetrical Diels-Alder adducts comprised of diene and dienophile of equal masses are recognized in mixtures using the scan function m2 = (1/2)m1.

Notes: Flavor enhancing nucleotides may be produced by streptomycetes. Mutants of streptomyces 772 were found to produce, under ordinary fermentation conditions, considerable amounts of 5′-IMP and 5′-XMP, but only traces of 5′-GMP. This was probably due to the feedback inhibition of the end product GMP. It was shown that through suitable fermentation techniques it was possible to overcome this internal control mechanism, leading to increased yields of 5′-GMP.

Notes: Admixing of several antibiotic powders which were insoluble in methyl methacrylate did not decrease the compressive and diametral tensile strengths of two acrylic bone cements when tested after setting for 1 day and after leaching 40 days in water at 37°C. When antibiotics were added as water solutions, the included water resulted in a significant decrease in these bulk mechanical properties.Storage in water for 40 days caused surface irregularities only on specimens of the set antibiotic admixtures. Approximately 0.5% of the admixed dosage of these water-soluble antibiotics could be leached from the set cements. The observed surface channels, presumably left by the loss of antibiotic, suggest further study of surface-sensitive mechanical properties may be needed.The bulk mechanical strengths presented here are conclusive only for the particular combinations of antibiotics and cements investigated, and should not be generalized at this time to any or all antibiotic admixtures or other mechanical properties.