Inhibitory receptors

Figure 1.3 Some possible basic neurotransmitter-synaptic arrangements for the excitation and inhibition of different neurons, (a) The single NT activates neuron B and inhibits neuron C by being able to activate both excitatory and inhibitory receptors or, more probably, acting on one receptor linked to both events. There is potential, however, for the NT to activate any inhibitory receptors that may be on B or excitatory receptors on C. (b) The same NT is used as in (a) but the excitatory receptors are now only on dendrites and separated from the inhibitory receptors only on the soma. There is less chance of unwanted mixed effects, (c) Neuron A releases distinct excitatory and inhibitory NTs from its two terminals each acting on specific and morphologically separated receptors. But this depends on a neuron being able to release two NTs. (d) Neuron A releases the same NT from both terminals. It directly excites B but inhibits C through activating an inhibitory interneuron (I) which releases an inhibitory NT onto specific receptors on C. This last scheme (d) is clearly more functional and is widely used...

Block the action of DA on similar inhibitory receptors on the DA neuron cell body itself... 

There are also many neurotransmitter and hormone receptors that contribute to the fine control of cAMP formation by inhibition of adenylyl cyclase. The action of inhibitory receptors is mediated by several different forms of the Gai family, specifically the Gail, Gai2, Gai3, Gao and Goa subtypes. The Ga subunits of these isoforms can inhibit the catalytic activity of adenylyl cyclase when the enzyme is activated by either Gas or forskolin. The inhibition of catalytic activity does not occur via competition with Gas but appears to occur by an interaction at a symmetric site on the AC molecule. Gai-mediated inhibition of adenylyl cyclase is most dramatic for AC5 and AC6. A few other forms of adenylyl cyclase, most notably AC1, can be inhibited by Gao but this effect is not as potent as the inhibition of AC5 and AC6 by Gai isoforms. The GTPase activity of Gai family members can be accelerated by a large family of RGS proteins (see Chapter 19). 

Electrical stimulation in the vicinity of the raphe nuclei has been reported to produce depressant effects on MSRs (32,142). These depressant effects could be attributed to activation of postsynaptic inhibitory receptors analogous to those characterized in the forebrain, except for the fact that the depression was blocked by 5-HT antagonists. The effectiveness of the antagonists suggests that the receptor is more akin to the excitatory 5-HT receptor characterized on motoneurons (134,184). The depressant behavioral effects could result from... 

Except for CD40, NK cell subsets showed different expression of killer-inhibitory receptors and costimulatory molecules between the polyal-lergic and healthy subjects. The study demonstrates that human NK cells comprise distinct receptor-expressing and cytokine-producing subsets similar to Thl and Th2 cells. These subsets of NK cells show differences in surface KIR receptors and costimulatory receptors and interfere with immunoglobulin regulation [34]. 

Bertone S, Schiavetti F, Bellomo R, Vitale C, Ponte M, Moretta L, Mingari MC Transforming growth factor-p-induced expression of CD94/NKG2A inhibitory receptors in human T lymphocytes. Eur J Immunol 1999 29 23. 

Sumatriptan and the other triptans are selective agonists for 5-HT1D and 5-HT1B receptors the similarity of the triptan structure to that of the 5-HT nucleus can be seen in the structure below. These receptor types are found in cerebral and meningeal vessels and mediate vasoconstriction. They are also found on neurons and probably function as presynaptic inhibitory receptors. 

In conclusion, the distribution of H3 receptors and the effects of lesions are consistent with functional studies showing that they are inhibitory receptors not only on histaminergic nerve terminals, but also on various aminergic and non-aminergic cerebral neurons and therefore they may be involved in a large variety of functions. 

Where the D2-like inhibitory receptor was identifed further it was mostly D2, D3 in rat nucleus accumbens, and never D4 (Table 1). The D3 receptor was thought to play a minor role also in the mouse corpus striatum (Joseph et al. 2002). However, this suggestion was refuted by the finding that no autoreceptor function remained in mouse striatum after genetic deletion of the D2 receptor (Schmitz et al. 2002). 

The results of Mizuno et al. (2007) make it likely that modulation of Ca2+ currents underlies the various modulations of GABA release. This view is supported by other studies for both D2-like inhibition (Pisani et al. 2000 Momiyama and Koga 2001) and Di-like facilitation (Arias-Montano et al. 2007). The D2-like inhibitory receptors presumably couple to Gi/o (Momiyama and Koga 2001), whereas the Di-like facilitatory receptors presumably couple to Gs, activation of adenylyl cyclase and activation of protein kinase A (Arias-Montano et al. 2007). The riddle of the exceptional cases of inhibition through Di-like receptors remains. For example, in rat prefrontal cortex Di-like receptors presynaptically inhibited GABAergic transmission, an effect blocked by an inhibitor of protein kinase A (Gonzalez-Islas and Hablitz 2001) - the same enzyme involved in facilitation through Di-like receptors... 

These are the only terminals where Boehm andDorostkar (in this Handbook) accept 5-HT3 receptors with confidence. As to G protein-coupled receptors, 5-HTi -like inhibitory receptors - where subclassilied 5-HTiA, 5-HTiB or 5-HTid - are common (Table4). A comparative study detected them in human (5-HTid) but not rabbit neocortex (Feuerstein et al. 1996b). 

The adenosine modulation of synaptic transmission exceeds the simple direct control of neurotransmitter release. Adenosine may have a permissive effect on responses to other presynaptic modulators, may regulate the rate of desensitization of other presynaptic receptors, or prevent an excessive influence of inhibitory receptors. In this respect it is often viewed as a modulator of modulators involved in the fine-tuning of neurotransmitter release. 

In most cases, mutual influences between presynaptic receptors have been explained by a cross-talk of intracellular signalling pathways. In several synapses, presynaptic actions of Ai receptors and other release-inhibitory receptors are mu-... 

Fresco P, Diniz C, Queiroz G et al (2002) Release inhibitory receptors activation favours the A2A-adenosine receptor-mediated facilitation of noradrenaline release in isolated rat-tail artery. Br J... 

Queiroz G, Talaia C, Genoa Ives J (2003a) Adenosine A2A receptor-mediated facilitation of noradrenaline release involves protein kinase C activation and attenuation of presynaptic inhibitory receptor-mediated effects in the rat vas deferens. J Neurochem 85 740-8 Queiroz G, Talaia C, Gonpalves J (2003b) ATP modulates noradrenaline release by activation of inhibitory P2Y receptors and facilitatory P2X receptors in the rat vas deferens. J Pharmacol Exp Ter 307 809-15... 

Transmitter Inhibitory Receptor Subtype Facilitatory Receptor Subtype... 

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