False adrenergic transmitters release

S.2.9.2. Formation, Storage and Release of False Adrenergic Transmitters 52.9.2.1. Biosynthesis of False Transmitters... 

Octopamine (4.41), which carries a p-hydroxyl group, is taken up even more readily into storage vesicles and is, in turn, released when the neuron fires. As an adrenergic agonist, octopamine is, however, only about one-tenth as active as NE therefore, it acts as a very weak neurotransmitter. Compounds such as this behave like neurotransmitters of low potency, and are called false transmitters. On the other hand, octopamine may be a true transmitter in some invertebrates, with receptors that cannot be occupied either by other catecholamines or by serotonin. 

Methyldopa (l -pathway directly parallels the synthesis of norepinephrine from dopa illustrated in Figure 6-5. Alpha-methylnorepinephrine is stored in adrenergic nerve vesicles, where it stoichiometrically replaces norepinephrine, and is released by nerve stimulation to interact with postsynaptic adrenoceptors. Flowever, this replacement of norepinephrine by a false transmitter in peripheral neurons is not responsible for methyldopa s antihypertensive effect, because the a-methylnorepinephrine released is an effective agonist at the cx adrenoceptors that mediate peripheral sympathetic constriction of arterioles and venules. In fact, methyldopa s antihypertensive action appears to be due to stimulation of central a adrenoceptors by a-methylnorepinephrine or a-methyldopamine. 

The action of tyramine on nerve receptors is mainly indirect by release of norepinephrine and dopamine from neuronal storage sites (363, 384). Tyramine and its /3-oxidized counterpart octopamine have been referred to as false neurotransmitters because these compounds can be taken up, stored, and released from nerve endings in a way similar to those of the principal neurotransmitters norepinephrine and dopamine (385). Octopamine was first discovered in salivary glands of octopods (386). The compound is widely distributed in the animal kingdom and is present in high amounts in the nervous system of several species of invertebrates such as molluscs and arthropods, where it acts as a specific transmitter substance (387). Octopamine may also play a role in the regulation of adrenergic neurotransmission in mammals (387). Administration of octopamine to intact animals produces a transient rise in blood pressure (388). 

Many foods and beverages (e.g., wine, cheese, and chocolate) contain tyramine. This chemical is normally degraded by MAOa, before systemic absorption. When the inhibition of MAOa occurs, due to the administration of these drugs, tyramine from ingested food is absorbed. It is then taken up into adrenergic neurons, where it enters the synthetic pathway and is converted to octopamine. a false transmitter. This results in a massive release of norepinephrine, and may result in a hypertensive crisis. 

It was demonstrated that in patients taking methyldopa, a-methylnorepinephrine is formed, stored and released as a "false transmitter" as in animals. Tests of adrenergic function in rats at the time of maximum blood pressure reduction failed to show sufficient impairment to account for the hypotension. However, the false transmitter principle may still apply to the action on central neuronsi ... 

Various foreign amines which are stored by adrenergic nerves are released in response to nerve stimulation. There is a very interesting correlation between the requirements for release of a false transmitter and the requironoits outlined above for storage. It seems that only those compounds whose structure is suitable to allow their retention within the intraneuronal storage vesicles are released during nerve activity (Table 18). 

A second factor is that the presence of the false transmitter may alter the responsiveness of the effector tissue to NA and other agonists. One mechanism by which this may occur is an inhibition of the neuronal uptake mechanism by the false transmitter, a-methylated amines, in particular, are very potent inhibitors of this transport process, and in tissues containing these false amines responsiveness to N A is increased. As far as the overall effect of the false transmitter is concerned, this will tend to reduce the effect on adrenergic transmission, since the increased responsiveness of the effector tissue may counteract the effect of a diminished release of NA. 

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