Inhibitory autoreceptor , presynaptic nerve

H3-receptors have been identified in the central nervous system. They are located on presynaptic membranes and serve as inhibitory autoreceptors at histaminergic neurons. They are also found on certain human autonomic nerve endings and in atrial tissue where they may inhibit norepinephrine release during ischemia. 

Heteroreceptors (HRs), like autoreceptors, can either suppress (inhibitory autoreceptors such as the tt2-adrenergic) or enhance the release of neurotransmitters. They are termed heteroreceptors since they are activated by neurotransmitters (e.g. norepinephrine) different from those produced by the nerve on which they are located (e.g. serotonergic). There might be numerous different heteroreceptors that bind various neurotransmitters on a single nerve. Table 1.2 summarizes some of the main modulating mechanisms relevant to intact functioning of the presynaptic nerve. Psychotropic medications can either enhance or suppress many of the major processes or modulatory events listed in this chapter. - ... 

The principle of negative feedback control is also found at the presynaptic level of autonomic function. Important presynaptic feedback inhibitory control mechanisms have been shown to exist at most nerve endings. A well-documented mechanism involves an 2 receptor located on noradrenergic nerve terminals. This receptor is activated by norepinephrine and similar molecules activation diminishes further release of norepinephrine from these nerve endings (Table 6-4). Conversely, a presynaptic Breceptor appears to facilitate the release of norepinephrine. Presynaptic receptors that respond to the transmitter substances released by the nerve ending are called autoreceptors. Autoreceptors are usually inhibitory, but many cholinergic fibers, especially somatic motor fibers, have excitatory nicotinic autoreceptors. 

Both mianserin and mirtazapine are antidepressant drugs which possess central 0C2 adrenoceptor blocking properties (pA2 7.3). However, mirtazapine is much more potent at histamine Hi receptors (pA2 9.1) and at 5-HT2 and 5-HT3 receptors (pA2 8.2). Blocking of Hi receptors explains the main side effects of mirtazapine, which produces marked sedation and weight gain. Blockade of presynaptic inhibitory 0C2 autoreceptors increases the release of NA, while blockade of presynaptic 0C2 inhibitory heteroreceptors on serotonin nerve terminals (Table 2) is likely to increase the release of serotonin. 

CNS Autoreceotors for Norepinephrine (NE) - Though the concept of autoinhibition of NE release is not universally accepted,the consensus is that release of NE from sympathetic nerves is modulated through inhibitory a2 autoreceptors. By contrast, somadendritic a2-adreno-ceptors of central noradrenergic neurons inhibit firing.Release of H-amezinium from rat cortical noradrenergic axons has been advanced as a model for the study of the a2-autoreceptor hypothesis. There are a number of mechanisms possible for the link between presynaptic a2 adrenoceptor activation and transmitter release, in which a pivotal role for Ca2+ has been established.3.8 (tore recent data implicates inhibition of adenylate cyclase with receptor activation and subsequent attenuation of transmitter release. 

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