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Abstract
Activation of different types of G-protein-linked and ionotropic presynaptic receptors has been shown to regulate neurotransmitter release throughout the central and peripheral nervous systems. In the case of G-protein-linked receptors, three major mechanisms have been suggested: (a) inhibition of Ca channels in the nerve terminal; (b) the activation of presynaptic K channels, resulting in a reduction in the effectiveness of the action potential; and (c) direct modulation of one or more components of the neurotransmitter vesicle release apparatus. In the case of ionotropic presynaptic receptors, inhibition of release may be achieved through depolarization of the terminal and inactivation of Na and Ca channels. Activation of presynaptic ionotropic receptors that are appreciably Ca permeable can also enhance the release of transmitters as a result of their ability to raise [Ca]i in the terminal directly. Many transmitters employ several of these mechanisms, thus allowing considerable flexibility in the presynaptic regulation of transmitter release.