Uptake and binding of some neurotransmitter substances and their analogues in the developing cerebellum of normal rodents and neurologically mutant mice.

East, J. Malcolm (1981). Uptake and binding of some neurotransmitter substances and their analogues in the developing cerebellum of normal rodents and neurologically mutant mice. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000fcc6

Abstract

Cells dissociated from the postnatally developing rat cerebellum retain their high affinity carrier-mediated transport system for (3H) GABA (Kt = 1 .9 uM, V = 1.8 pmol per 106 cells per min.) and (3H) glutamate (Kt = 10 uM, V = 7.9 pmol per 106 cells per min.). Using a unit gravity sedimentation technique it was demonstrated that (3H) GABA was taken up principally into fractions which were enriched in such neuronal types as Purkinje, stellate and basket cells. (3H) 3-alanine (which is known to be taken up specifically by the glial GABA transport system) and (3H) glutamate were concentrated by cells of the same size range. (3H) glutamate uptake was minimal in fractions enriched in precursors of granule cells. These results are discussed in relation to reports of high affinity (3H) glutamate uptake by glia. The role of glutamate transport in glutamatergic cells is also considered.

In addition the development of GABA, 3-adrenergic and muscarinic acetylcholine receptors in the cerebella of weaver (wv), reeler, (rl) staggerer (sg) and jimpy (jp), neurological mutant mice and their normal counterparts was examined using the radioligands, (3H) muscimol, (3H) dihydroalprenolol ((3H) DHA) and (3H) quinuclidinylbenzilate ( (3H) QNB) . The maximum increase in ligand binding occurred during the period 15-20 days for (3H) muscimol, 10-15 days for (3H) DHA, 5-15 days for (3H) QNB. Binding of all ligands was significantly reduced with respect to controls in the cerebellar mutants, wv, rl and sg. (3H) Muscimol binding was the most affected (4-19 per cent control at 20 days) and (3H) QNB binding was least affected (36-50 percent control at 20 days). The corresponding figures for (3H) DHA were 14-22 percent. Binding of these ligands to jp tissue was not significantly different from control except for (3H) QNB binding which was 80 percent of control at 20 days. Binding of all ligands was saturable and of high affinity (muscimol Kd = 12.8 nM; DHA Kd = 0.26 nM; QNB Kd = 0.14 nM) and the affinity constants for binding did not change significantly during development. These data are discussed in relation to (i) the known pharmacology and development of cerebellar neurons and (ii) the effects of the mutations on the development of cerebellar neurons.

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