Heteroreceptors , presynaptic nerve

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. - ... 

Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6-4. Presynaptic regulation by a variety of endogenous chemicals probably occurs in all nerve fibers. 

In the first part of our chapter the occurrence of H3 heteroreceptors in the CNS and in the retina will be described. Then the location of the H3 heteroreceptors will be discussed. (The term "heteroreceptor" will be used in a relatively broad sense in this article, i.e. regardless of whether the presynaptic location on the nerve endings themselves has been proven or not.) Next, interactions between H3 heteroreceptors and other types of presynaptic receptors will be considered. Finally, some general remarks with respect to H3 heteroreceptors as targets for new drugs will be given. 

Table 1. Location of H3 heteroreceptors inhibiting the release of monoamines, acetylcholine and glutamate in the brain. To prove or disprove the presynaptic location of H3 receptors, transmitter release was studied in isolated nerve endings (synaptosomes) or in brain slices superfused with K+-rich Ca2+-free medium containing tetrodotoxin (TTX) (in the latter case, transmitter release was evoked by introduction of Ca2+ ions into the medium). The experimental approaches used in the electrophysiological study to show the presynaptic location of H3 receptors on glutamatergic neurones are described in the text.

Abstract Presynaptic receptors for dopamine, histamine and serotonin that are located on dopaminergic, histaminergic and sertonergic axon terminals, respectively, function as autoreceptors. Presynaptic receptors also occur as heteroreceptors on other axon terminals. Auto- and heteroreceptors mainly affect Ca2+-dependent exocytosis from the receptor-bearing nerve ending. Some additionally subserve other presynaptic functions. 

Compelling evidence indicates that a major function of GABAbRs is to mediate inhibition of neurotransmitter release from nerve terminals where they are localized as presynaptic auto- and heteroreceptors (see Bonanno and Raiteri 1993a Bowery et al. 2002 Raiteri 2006, for reviews). 

Fuder H, Muscholl E (1995) Heteroreceptor-mediated modulation of noradrenaline and acetylcholine release from peripheral nerves. Rev Physiol Biochem Pharmacol 126 265 412 Funahashi M, Mitoh Y, Matsuo R (2004a) Activation of presynaptic 5-HT3 receptors facilitates glutamatergic synaptic inputs to area postrema neurons in rat brain slices. Methods Find Exp Clin Pharmacol 26 615-22... 

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. 

The original observations made in the early 1970s led to the hypothesis that neurotransmitter release was regulated at the level of the nerve terminals by presynaptic auto- and heteroreceptors. These discoveries were confirmed and extended... 

When a stimulus depolarises the transmembrane potential in a spiking axon above the threshold level, an all-or-none action potential in a spiking axon is activated. The action potential propagates unattenuated to the nerve terminal where ion fluxes activate a mobilisation process leading to transmitter secretion.3 The neurotransmitter binds reversibly to receptor proteins embedded in the membrane of a neuron, which triggers a certain effect. There are two types of receptors known, presynaptic receptors or autoreceptors which are present on the neurotransmitter releasing neurons , and postsynaptic or heteroreceptors, which are present on the neurotransmitter receiving neuron . The former are supposed to perform a feed-back function, and slow down the release of neurotransmitter from these neurons when they are stimulated.4... 

B. Effects Angiotensin II is a potent arteriolar vasoconstrictor and stimulant of aldosterone release. All directly incTeases peripheral vascular resistance and, through aldosterone, causes renal sodium retention. All also facilitates the release of norepinephrine from adrenergic nerve endings via presynaptic heteroreceptor action. All of these effects are mediated by the angiotensin AT, receptor, a G, -coupled receptor. 

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