Glutamate and related amino acids in cat spinal roots, dorsal root ganglia and peripheral nerves.
TL;DR: The unique regional distribution of glutamate is consistent with the proposed role of this amino acid as an excitatory transmitter at the terminals of primary afferent fibres.
Abstract: —
Of the free amino acids found in extracts of cat spinal roots, dorsal root ganglia and peripheral nerves, only glutamate was present in disproportionately high concentrations in those parts of the dorsal roots between ganglia and spinal cord. This distribution suggests that the high dorsal root levels of glutamate may result from synthesis in dorsal root ganglia and subsequent transport towards the spinal cord. Four excitant amino acids were detected in the extracts: aspartate, cysteate, cysteine sulphinate and glutamate. The unique regional distribution of glutamate is consistent with the proposed role of this amino acid as an excitatory transmitter at the terminals of primary afferent fibres.
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01 Jan 1974TL;DR: Evidence for A m i n o Acids as T ransmi t t e r s as well as evidence for Synthesis and Storage are presented.
Abstract: 2. Evidence for A m i n o Acids as T ransmi t t e r s . . . . . . . . . . . . . . . . . . . . 99 2.1. Synthesis and Storage . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 2.2. Synapt ic Release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 2.3. Postsynapt ic Act ion . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 2.4. Postsynapt ic An tagon i s t s . . . . . . . . . . . . . . . . . . . . . . . . . 103 2.5. Inac t iva t ion and R e m o v a l . . . . . . . . . . . . . . . . . . . . . . . . . 104
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TL;DR: The concept that each nerve cell makes and releases only one nerve transmitter (widely known as Dale's Principle) has been re-examined and experiments suggesting that some nerve cells store and release more than one transmitter have been reviewed.
609 citations
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TL;DR: It is shown here that synaptic terminals in the superficial laminae of the spinal cord of rats selectively stain for the same glutamate antiserum, and that glutamate is the neurotransmitter in primary afferents mediating input from different peripheral receptor classes, including nociceptors.
Abstract: By light microscopic immunocytochemistry it has been previously shown that approximately equal to 70% of the neurons in rat dorsal root ganglia are labeled with an antiserum for glutamate conjugated to hemocyanin; the smaller among these neurons are also positive for substance P. By using a postembedding ImmunoGold method and electron microscopy, it is shown here that synaptic terminals in the superficial laminae of the spinal cord of rats selectively stain for the same glutamate antiserum. Immunolabeling is in small dome-shaped and in large scalloped synaptic terminals. Scalloped terminals are of two types. One type consists of dark terminals with many agranular vesicles of different size and a few large granular vesicles; these are probably endings of unmyelinated and small myelinated primary afferent fibers. The other type consists of light terminals with small agranular vesicles homogeneous in size with neurofilaments and many mitochondria; these are probably endings of larger myelinated primary afferent fibers. By means of double-labeling electron microscopic immunocytochemistry with colloidal gold particles of two different sizes, it is also shown here that substance P is present in only the dark type of glutamate-labeled scalloped terminals. The primary afferent origin of the terminals labeled by the antisera for glutamate and for substance P is demonstrated by a triple-labeling strategy: immunocytochemistry for both antisera on sections from rats in which dorsal rhizotomy or dorsal root ganglion injection of horseradish peroxidase conjugated to wheat germ agglutinin was performed. It is proposed that glutamate is the neurotransmitter in primary afferents mediating input from different peripheral receptor classes, including nociceptors. Effects of glutamate and substance P on spinal dorsal horn neurons may result from co-release of these two mediators from the same dorsal root afferent terminal.
578 citations
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TL;DR: Experiments suggest that several aminoacids, especially glycine and glutamic, aspartic and gamma-aminobutyric acids are neurotransmitters in the central nervous system, but careful subcellular and regional studies have not provided supporting neurochemical evidence.
Abstract: NEUROPHYSIOLOGICAL experiments suggest that several aminoacids, especially glycine and glutamic, aspartic and gamma-aminobutyric (GABA) acids, are neurotransmitters in the central nervous system1–3 But careful subcellular4,5 and regional studies6–8 have not provided supporting neurochemical evidence, because ammo-acids, with the possible exception of GABA, also have general metabolic functions in nervous tissue
284 citations
References
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TL;DR: A survey of the activity of compounds structurally related to both series of amino acids finds that one of them or a related substance may have excitatory transmitter function within the nervous system.
Abstract: THE anions of aspartic and glutamic acids have potent excitatory action upon spinal neurones (CURTIS, PHILLIS and WATKINS, 1960); this is in marked contrast to the strongly depressant action exhibited by their respective a-decarboxylation products, 0-alanine and y-amino-n-butyric acid (GABA) (CURTIS, PHILLIS and WATKINS, 1959). The latter amino acids cause no significant change in the membrane resting potential of motoneurones, which is strong evidence that these substances are not inhibitory transmitter agents within the mammalian spinal cord. On the other hand, the excitant amino acids cause depolarization of spinal neurones, and consequently one of them or a related substance may have excitatory transmitter function within the nervous system. This possibility has led to a survey of the activity of compounds structurally related to both series of amino acids.
831 citations
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TL;DR: Data is presented on the distribution of glutamate, glutamine, GABA, aspartate, and glycine in dorsal and ventral roots and four spinal cord areas in the cat and the relative merits of these compounds as possible spinal excitatory or inhibitory transmitters are discussed.
Abstract: IT IS now generally accepted that mediation of synaptic excitation and inhibition within the mammalian nervous system is chemical. The major excitatory or inhibitory transmitters acting on spinal motoneurons and interneurons have not been identified with certainty. For this reason, the iontophoretic studies of CURTIS and WATKINS (1960) are of great interest. They showed that certain amino acids cause excitation while others result in depression of neuronal activity when these compounds are applied in proximity to the external surfaces of spinal neurons. For instance, the excitatory effects of L-glutamic acid and L-aspartic acid and the inhibitory effects of GABA and glycine are 'transmitter-like' in their rapidity of action, quick reversibility, and the great scnsitivity of the neurons to small quantities of these agents. These observations have been confirmed in our laboratories. Similar actions of these amino acids were shown in other parts of the central nervous system (see KRNJEVIC, 1965, for references). These findings suggest a role for amino acids as synaptic transmitters, the point of departure of our research. In this paper, we present data on the distribution of glutamate, glutamine, GABA, aspartate, and glycine in dorsal and ventral roots and four spinal cord areas in the cat. On the basis of these findings, we discuss the relative merits of these compounds as possible spinal excitatory or inhibitory transmitters. Preliminary reports of several aspects of this study have been published (APRISON, GRAHAM, BAXTER and WERMAN, 1965a; APRISON, GRAHAM, LIVENGOOD and WERMAN, 196%; APRISON and WERMAN, 1965). E X P E R I M E N T A L Preparation of tissue. Tissue was obtained from mature cats (2-4 kg) as follows: under nernbutal anaesthesia, laminectomy of the upper sacral and lower lumbar spine was carried out. The spinal roots were identified by size and site of dural penetration. The dura was opened, spinal fluid drained, and lumbar 6 and 7 and sacral 1 dorsal and ventral roots were isolated and removed. The ventral roots were always excised first. The roots were rinsed in saline, blotted quickly on filter paper, and immediately frozen on dry ice. Thin sections (2-3 mm) of the cord were cut and frozen on dry ice. After wrapping in aluminum foil and labelling, the samples were stored at -23\" to -28\" until used, In some of the earlier experiments, the sections were taken from the freezer and placed on a slab
360 citations
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TL;DR: The argument is strongly in favor of the conclusion that among d.r.C fibers, as in other fibers, there is no cross-excitation between the axons, and the view is confirmed that the velocities of conduction in the fibers can be precisely accounted for by multiplying the diameters by a constant.
Abstract: As an aid in the interpretation of the physiological properties of unmedullated nerve fibers, particularly those having their cells of origin in the dorsal root ganglia, more precise information about their morphology has been acquired through employment of the electron microscope. The appearance of the fibers in the skin nerves is described, with special reference to the structure of their sheaths; and a notation is made about the bearing of the axon-sheath relationship on the biophysical mechanism of conduction (p. 714). There is no basic difference between the sheath systems of the d.r.C and the s.C fibers. Attention is called to a point of similarity between the sheaths of unmyelinated and myelinated axons (p. 715). An assessment was made of the likelihood of interaction between the fibers. In action potentials showing temporal dispersion at several distances, the elevations appeared in their calculated positions. A model of a group of Schwann sheaths was constructed from successive electron microscope sections, showing that the lengths of the sheath branches are short in comparison with the wave lengths of the action potentials. Supported by these and other considerations, the argument is strongly in favor of the conclusion that among d.r.C fibers, as in other fibers, there is no cross-excitation between the axons. A new analysis of the size distribution of the fibers in a sural nerve was made from electron microscope pictures; and from the measurements the action potential was constructed. The result confirmed the view, previously expressed, that the velocities of conduction in the fibers can be precisely accounted for by multiplying the diameters by a constant. In the dorsal roots, the striking change that takes place in the appearance of the fibers and their disposition in the Schwann sheaths can be seen in Fig. 11. The axons partake of the special properties of the peripheral branches, which necessitated the creation of the subdivision of d.r.C fibers. But, their diameters are much smaller. At a set of reduced conduction velocities the configuration of the compound action potential in the nerves is repeated in the roots, with the root velocities still conforming to the size-velocity rule derived from nerve axons.
285 citations