| One of the unique chemical characteristics of the brain is the massively high density of synapses between different neurons, at which a locally acting neurohormone is released by one axon onto many other cell bodies. On the receiving end, a given cell body will typically receive a myriad of cellular products via its profusely branched dendritic tree: each branch can be smothered in synapses. The first chemical messenger or 'neurotransmitter' to traverse the synaptic cleft is the neurohormone, which is released by the axon of the first cell onto the dendrite of the second cell. This action is mediated by a neurotransmitter receptor on the respondent cell. There is usually a second messenger such as a cyclic nucleotide, which may also lead to a third messenger such as a phosphorylated protein. Typically, G-proteins are found just under the neurotransmitter receptor protein spanning the cell membrane, where they act to 'couple' the first messenger (e.g. norepinephrine) to a second messenger (e.g. cyclic AMP [cAMP]) (see also Chapter 38).
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| A 75-year-old woman complained of postural dizziness, dry mouth, intermittent diarrhea, and numbness in both her feet. On examination, there was a marked decrease in blood pressure on assuming the upright posture. A chest radiogram revealed lytic lesions in the sternum. Her urine contained Bence-Jones protein. A bone marrow examination demonstrated increased numbers of plasma cells (see also Chapter 3). |
| Comment. Her neurological condition was caused by amyloidosis in which the free light-chain component of myeloma globulin produced by tumor of plasma cells in the bone marrow, accumulates in peripheral nerves. The light chains adopt the configuration of a β-pleated sheet, with multiple copies that are intercalated and resistant to normal proteolysis. |
| Neurotransmitters are normally inactivated after their postsynaptic actions on the target cell, hydrolysis being a
major mechanism by which this is achieved. The best studied example is that of the enzyme, acetylcholinesterase. There can also be blockade at the level of the second messenger, such as cAMP, which is broken down by the enzyme phosphodiesterase. This enzyme is inhibited by methylxanthines and caffeine, and thereby mimics many of the effects of adrenergic neurotransmission.
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| Synaptic transmission also involves the recycling of membrane components
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| In addition to release of a specific neurohormone, there is also an extensive system for recycling of membrane constituents associated with this process. The synaptic vesicles contain a very high concentration of the relevant neurotransmitter, which is bounded by a membrane (see Chapter 40). During synaptic release of the transmitter, there is fusion of the synaptic vesicle membrane (containing the neurotransmitter) with the presynaptic membrane. This increase in total membrane mass is redressed by invagination of the lateral aspects of the nerve terminals, where an inward puckering movement of the membrane is effected by contractile movements of the protein, clathrin. There then follows a form of pinocytosis of the excess membrane, which is transported in retrograde fashion toward the nucleus, to be digested in lysosomes.
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