Muscarinic activity, control

Bieger D. (1984). Muscarinic activation of rhombencephalic neurones controlling oesophageal peristalsis in the rat. Neuropharmacology. 23(12A) 1451-64. 

Clinical signs and symptoms of toxicity are related to the overstimulation of muscarinic, nicotinic, and central nervous system receptors in the nervous system. Muscarinic receptors are those activated by the alkaloid drug muscarine. These receptors are under the control of the parasympathetic nervous system, and their hyperactivity results in respiratory and gastrointestinal dysfunction, incontinence, salivation, bradycardia, miosis, and sweating. Nicotinic receptors are those activated by nicotine. Hyperactivity of these receptors results in muscle fasciculations even greater stimulation results in blockade and muscle paralysis (Lefkowitz et al. 1996 Tafliri and Roberts 1987). Hyperactivity of central nervous system receptors results in the frank neurological signs of confusion, ataxia, dizziness, incoordination, and slurred speech, which are manifestations of acute intoxication. Muscarine and nicotine are not... 

Figure 17.7 Possible mechanism by which atypical neuroleptics with antimuscarinic activity produce few EPSs. Normally the inhibitory effects of DA released from nigrostriatal afferents on to striatal neuron D2 receptors is believed to balance the excitatory effect of ACh from intrinsic neurons acting on muscarinic (M2) receptors (a). Typical neuroleptics block the inhibitory effect of DA which leaves unopposed the excitatory effect of ACh (b) leading to the augmented activity of the striatal neurons and EPSs (see Fig. 15.2). An atypical neuroleptic with intrinsic antimuscarinic activity reduces this possibility by counteracting the excitatory effects of released ACh as well as the inhibitory effects of DA (c). Thus the control of striatal neurons remains balanced...

Muscarinic M2 receptor CHRM2 Agonism Vagal effects (key role in the control of heart rate and smooth muscle activity) Bradycardia. Antagonism May induce cardiac side effects (palpitations, dysrhythmia) or peripheral edema, bronchoconstriction can result from presynaptic M2 receptor antagonism if postsynaptic M3 receptors are not also blocked. 

A. Control recording showing the spontaneous diastolic depolarization. B. The effect of norepinephrine is to increase the slope of diastolic depolarization. The frequency of spontaneous discharge is increased. This effect is mediated through the activation of p-adrenoceptors in sinoatrial nodal cells. C. Acetylcholine stimulates muscarinic receptors in sinoatrial nodal cells. 

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). 

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