Essays in neurochemistry and neuropharmacology最新文献

From the above, it doesn't seem too rash now to elevate octopamine to the status of a neuroregulator in the invertebrates. To encapsulate, octopamine occurs in high concentration in many higher invertebrates and is found in specific octopaminergic neurons from which it is released upon stimulation. It then interacts with specific receptors, some of which at least, are linked to adenylate cyclase. The action of octopamine is then terminated by re-uptake or by N-acetylation (or a combination of these functions). It is fair to say we know as much about octopamine and its role as a neuromodulator in vertebrates as we do about noradrenaline in vertebrates-only our ignorance isn't as well documented. But where does octopamine fit into the scheme of Barchas et al. (1978)? We can agree that it is a neuroregulator but is it a neurotransmitter or a neuroregulator? Turning to the three well characterized octopaminergic systems, these all seem to be neuromodulatory in nature. Clearly the octopaminergic neurons in the lobster which release octopamine into the haemohymph fall into the neuromodulator class. In the case of the octopaminergic neurons in the adult firefly lantern, octopamine released from these neurons appears to interact with a specific adenylase cyclase-linked receptor and this leads to a response, the flash of the lantern. This therefore appears to be a situation where octopamine is a neurotransmitter, not dependent on other transmitters for actions (Nathanson, 1979). In the system of octopaminergic neurons which originate in the DUM neurons and innervate skeletal muscle, octopamine again appears to be a neuromodulator, altering the response of the muscle to another neurotransmitter (O'Shea and Evans, 1979). However, these peripheral octopaminergic system probably form only a small portion of the octopaminergic neurons in arthropods. The role of octopamine in the central nervous system must remain conjectural for the present.

In the essay we have described what we consider to be criteria for the selection of a simple mammalian model system for studying synaptic mechanisms and have shown how the dopamine-containing amacrine neuronal system of the rat retina fit these criteria. Thus, the retina contains a defined population of neurons which secrete dopamine. The neuronal activity of the dopamine-containing cells can be reproducibly controlled by the experimenter using a physiological stimulus, light. The neurons are activated by exposure to light and are relatively quiescient in the dark. We have described how this model system has been employed to study the regulation of dopamine synthesis in response to both short term and long term changes in neuronal activity. Short term exposure to light increases dopamine turnover and activates tyrosine hydroxylase, which is characterized by a decrease in the Km of the enzyme for the pteridine cofactor. After long term exposure to light the Km for the cofactor returns to the value found for animals in the dark, while the Vmax of the enzyme increases. The change of Vmax is the consequence of an increase in the specific activity of the enzyme. Evidence has also been presented illustrating the usefulness of the dopamine neuronal system of retina for studying postsynaptic mechanisms. Retina appears to contain only D-1 receptors, which are linked to adenylate cyclase. Since dopamine release in the retina can be experimentally manipulated by light, it may be possible to study the consequence of prolonged activation of receptors by dopamine on postsynaptic biochemistry.