Acetylcholine release autoreceptors

Roth, M. T., Fleegal, M. A., Lydic, R. Baghdoyan, H. A. (1996). Pontine acetylcholine release is regulated by muscarinic autoreceptors. Neuroreport 7, 3069-72. 

Douglas, C. L., Baghdoyan, H. A. Lydic, R. (2001). M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse. 

The pertussis toxin sensitivity and, hence, Gi/o coupling of 5-HTib autoreceptors in rat striatum (Section4.1) and of the 5-HTib heteroreceptors inhibiting dopamine release in rat striatum (Section4.4) also holds true for the 5-HTib heteroreceptors inhibiting acetylcholine release in rat hippocampus (Sarhan and Fillion 1999). Presynaptic HT4 receptors increase cAMP levels which in turn, by stimulating protein kinase A, may inhibit K+ channels to enhance transmitter release (Eglen et al. 1995). 

In the peripheral (Wessler 1989) as well as central (Wonnacott 1997) nervous system, presynaptic nicotinic autoreceptors were reported to control the release of acetylcholine. In both locations, the consequence of presynaptic nAChR activation most commonly is an increase in both spontaneous and evoked acetylcholine release (MacDermott et al. 1999), whereas presynaptic muscarinic receptors mediate the opposite effect, an autoinhibition. Recent studies have focused on the composition of presynaptic nAChRs (Table 2). In the hippocampus, nicotinic autoreceptors were suggested to be a3/p4 receptors (Tani et al. 1998), but a role of p2 subunits has also been implicated (Lloyd et al. 1998). Likewise, in the neocortex, presynaptic nicotinic autoreceptors are likely to be 04/ p2 receptors (Marchi et al. 2002). In contrast, in the interpeduncular nucleus the autoreceptors were suggested to mainly contain a3 and p4 subunits (Grady et al. 2001). 

Nords trom, O., and Bartfai, T. (1981). 8-Br-cyclic GMP mimics activation of muscarinic autoreceptor and inhibits acetylcholine release from rat hippocampal. slices. Brain Res. 213, 467-171. 

The M2 receptors are found in abundance in the heart, where their activation exerts both negative chronotropic and inotropic actions. In smooth muscle, they stimulate contraction. Activation of M2 autoreceptors located on nerve terminals affords neural inhibition by decreasing acetylcholine release. 

To date, five subtypes of these receptors have been cloned. However, initial studies relied on the pharmacological effects of the muscarinic antagonist pirenzepine which was shown to block the effect of several muscarinic agonists. These receptors were termed Mi receptors to distinguish them from those receptors for which pirenzepine had only a low affinity and therefore failed to block the pharmacological response. These were termed M2 receptors. More recently, M3, M4 and M5 receptors have been identified which, like the Mi and M2 receptors occur in the brain. Recent studies have shown that Mi and M3 are located posts)maptically in the brain whereas the M2 and M4 receptors occur pres)maptically where they act as inhibitory autoreceptors that inhibit the release of acetylcholine. The M2 and M4 receptors are coupled to the inhibitory Gi protein which reduces the formation of cyclic adenosine monophosphate (cyclic AMP) within the neuron. By contrast, the Mi, M3 and M5 receptors are coupled to the stimulatory Gs protein which stimulates the intracellular hydrolysis of the phosphoinositide messenger within the neuron (see Figure 2.8). 

Histamine H3-receptors have been reported to regulate not only the release and turnover of histamine via autoreceptors on histaminerglc nerve endings [1-3], but also the releases of noradrenaline, dopamine, serotonin, and acetylcholine via heteroreceptors on non-histaminerglc axon terminals [22-26], Thioperamide increased the release of these neurotransmitters, while... 

In addition to their functions as presynaptic autoreceptors, 0C2AR can also modulate release of other neurotransmitters (Figure 3). In the CNS, 0C2A and 0C2C receptors inhibit dopamine release in basal ganglia (Bucheler et al. 2002) as well as serotonin secretion in mouse hippocampus and brain cortex (Scheibner et al. 2001a). In the enteric nervous system, the release of acetylcholine as determined by [3H] -choline overflow from tissue slices was selectively inhibited by (X2aAR (Scheibner et al. 2002). 

Dopamine autoreceptors play a role in Parkinson s disease, schizophrenia and drug addiction. Dopamine heteroreceptors affecting the release of acetylcholine and of amino acid neurotransmitters in the basal ganglia are also relevant for Parkinson s disease. Peripheral dopamine heteroreceptors on postganglionic sympathetic terminals influence heart rate and vascular resistance through modulation of noradrenaline release. 

D2-like receptors couple mainly to Gi/o proteins, as mentioned above. However, there is no direct evidence to support this coupling for the release-modulating autoreceptors. Moreover, the subsequent intracellular signal transduction has never been studied directly in axon terminals. Mouse AtT-20 pituitary cells, which release acetylcholine and adrenocorticotropic hormone, have been used as a model for axon terminals. When expressed in these cells, D3 receptors mediated inhibition of P/Q-type calcium channels and activation of G protein-coupled inward rectifier potassium channels (Kuzhikandathil et al. 1998 Kuzhikandathil and Oxford 1999). Both would explain the autoreceptor-mediated inhibition of dopamine exocytosis. 

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