Neurochemical and pharmacological correlates of inferior olive destruction in the rat: attenuation of the events mediated by an endogenous glutamate-like substance.
The effects of a lesion of the inferior olive (the source of climbing fibres) has been investigated on a number of parameters of cerebellar excitatory amino acid function. Protoveratrine elicits a large increase in guanosine cyclic 3',5'-monophosphate levels in cerebellar slices, probably through the release of excitatory amino acids such as glutamate or aspartate, since the receptors involved are susceptible to specific antagonists. While the direct stimulatory (postsynaptic) effects of glutamate and related amino acids were not altered after loss of climbing fibres induced by 3-acetylpyridine, the guanosine cyclic 3',5'-monophosphate response to protoveratrine was markedly (40%) attenuated. Concomitant with this was a similar reduction in the high-affinity uptake of D-[3H]aspartate, a proposed marker for glutamate/aspartate terminals. Experiments to investigate the calcium-dependent, potassium-stimulated release of glutamate and aspartate, failed to reveal any reduction following acetylpyridine lesions. Although this latter finding does not exclude the possibility that these amino acids could be the transmitter of the climbing fibres, our data would rather suggest the involvement of some glutamate-like, but as yet unidentified, neuroexcitatory substance.
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001931:Brain Mapping; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000502:physiology*; D018698:Glutamic Acid; D009412:Nerve Fibers / Q000502:physiology; D009847:Olivary Nucleus / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000502:physiology
D005971:Glutamates; D011725:Pyridines; C010835:3-acetylpyridine; D001224:Aspartic Acid; D018698:Glutamic Acid; D006152:Cyclic GMP