Presynaptic or prejunctional receptors are located on the presynaptic nerve endings and function to control the amount of transmitter released per nerve impulse and in some instances to affect the rate of transmitter synthesis through some as yet undetermined feedback mechanism. For instance, during repetitive nerve stimulation, when the concentration of transmitter released into the synaptic or junctional cleft is relatively high, the released transmitter may activate presynaptic receptors and thereby reduce the further release of transmitter. Such an action may prevent excessive and prolonged stimulation of the postsynaptic cell. In this case, the activation of the presynaptic receptor would be part of a negative feedback mechanism.
The presynaptic receptors may have pharmacological significance, since several drugs may act in part either by preventing the transmitter from reaching the presynaptic receptor, thus causing excessive transmitter release, or by directly stimulating presynaptic receptors and thereby diminishing the amount of transmitter released per impulse.
The inhibitory presynaptic a-adrenoceptors found on noradrenergic neurons are of the a2-subtype. Adrenoceptors of the (32 subclass also occur presynap-tically, and activation of these receptors leads to enhanced norepinephrine release. The physiological and pharmacological importance of these presynaptic p2-receptors is less certain than it is for presynaptic a2-receptors.
Presynaptic receptors for nonadrenomimetic substances (e.g., acetylcholine, adenosine) also have been found on the sympathetic presynaptic nerve ending. Their importance and role in the modulation of neurotransmission have not been definitively established.
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