58
5
What You Will Learn in This Chapter
In this chapter we will describe the physiological and psychological activities of some
prominent plant derived compounds that target components of GPCR-signalling pathways.
These include ephedrine and reserpine, muscarine, atropine and physostigmine, caffeine,
cannabis, cocaine, morphin and some hallocinogenic drugs.
5.1 Muscarinic Acetylcholine Receptors (MAchR): Muscarine,
Atropine and Physostigmine
Acetylcholine is, besides noradrenalin, the major neurotransmitter in the parasympathetic and sympathetic nervous systems. It is discharged at all preganglionic synapses and
most postganglionic nerve endings of the parasympathetic nervous system; see . Fig. 5.1.
Sympathetic postganglionic neurons connected to perspiratory glands also use acetylcholine. Moreover, it is the neurotransmitter at all neuromuscular junctions connecting neurons with skeletal muscle cells. In the brain, acetylcholine is used in the cholinergic
inhibitory neurotransmitter system and as a neuromodulator for neuronal pathways governing plasticity, sensory perceptions upon waking up, sustained attention, promotion of
REM sleep and memory.
Acetylcholine activates two different kinds of receptors, GPCRs, agonized by muscarine and called muscarinic acetylcholine receptors (MAchR), and ion channels, agonized
by nicotine and called nicotinic acetylcholine receptors (NAchR). In ganglia of both, parasympathetic and sympathetic nerve endings nicotinic receptors are found. These will be
discussed later. Postganglionic parasympathetic neurons use muscarinic receptors for
neurotransmission. Substances mimicking the action of acetylcholine on postganglionic
parasympathetic neurons are therefore parasympathicomimetics. These include the
mushroom toxin muscarine after which the receptor is named (see 7 Chap. 3). Substances
blocking the action of acetylcholine are parasympatholytic. The plant tropane-alkaloid
atropine is the most prominent example (see 7 Chap. 3).
Moreover, MAchRs are expressed in different brain areas, and their signalling is
involved in neuronal networks for processes of attention, learning and memory.
There are five isoforms of MAchRs. Of those, M1, M3 and M5 are coupled to G q/11 and
phospholipase C (PLC). Thus, their activation induces Ca 2+ efflux from the endoplasmic
reticulum and activation of protein kinase C (PKC). M2 and M4 are coupled to G i thus
inhibiting adenylyl cyclase. The G i β/γ-subunits activate GIRK channels (inwardly rectifying K + -channels) and induce hyperpolarization. M2 is localized at the heart and is important for control of heartbeat and rhythm. In pacemaker cells the “funny current” or
pacemaker current, which is a result of the opening of “hyperpolarization-activated cyclic
nucleotide-gated cation channels” (HCN), is inhibited by the acetylcholine
signalling- induced decrease in cAMP. The opening of GIRK channels makes it harder for
the pacemaker cells to be depolarized. Physiologically this is important for maintenance
of the regular heartbeat (Kruse et al. 2014); see . Fig. 5.2.
Many synthetic compounds have been developed to block MAchR signalling, e.g. benztropine (trade name Cogentin), which is used to treat symptoms of Parkinson’s disease,
and so-called long-acting muscarinic receptor antagonists LAMAs like aclidinium, glyChapter 5 · GPCRs as Targets for Plant-Derived Drugs
5
What You Will Learn in This Chapter
In this chapter we will describe the physiological and psychological activities of some
prominent plant derived compounds that target components of GPCR-signalling pathways.
These include ephedrine and reserpine, muscarine, atropine and physostigmine, caffeine,
cannabis, cocaine, morphin and some hallocinogenic drugs.
5.1 Muscarinic Acetylcholine Receptors (MAchR): Muscarine,
Atropine and Physostigmine
Acetylcholine is, besides noradrenalin, the major neurotransmitter in the parasympathetic and sympathetic nervous systems. It is discharged at all preganglionic synapses and
most postganglionic nerve endings of the parasympathetic nervous system; see . Fig. 5.1.
Sympathetic postganglionic neurons connected to perspiratory glands also use acetylcholine. Moreover, it is the neurotransmitter at all neuromuscular junctions connecting neurons with skeletal muscle cells. In the brain, acetylcholine is used in the cholinergic
inhibitory neurotransmitter system and as a neuromodulator for neuronal pathways governing plasticity, sensory perceptions upon waking up, sustained attention, promotion of
REM sleep and memory.
Acetylcholine activates two different kinds of receptors, GPCRs, agonized by muscarine and called muscarinic acetylcholine receptors (MAchR), and ion channels, agonized
by nicotine and called nicotinic acetylcholine receptors (NAchR). In ganglia of both, parasympathetic and sympathetic nerve endings nicotinic receptors are found. These will be
discussed later. Postganglionic parasympathetic neurons use muscarinic receptors for
neurotransmission. Substances mimicking the action of acetylcholine on postganglionic
parasympathetic neurons are therefore parasympathicomimetics. These include the
mushroom toxin muscarine after which the receptor is named (see 7 Chap. 3). Substances
blocking the action of acetylcholine are parasympatholytic. The plant tropane-alkaloid
atropine is the most prominent example (see 7 Chap. 3).
Moreover, MAchRs are expressed in different brain areas, and their signalling is
involved in neuronal networks for processes of attention, learning and memory.
There are five isoforms of MAchRs. Of those, M1, M3 and M5 are coupled to G q/11 and
phospholipase C (PLC). Thus, their activation induces Ca 2+ efflux from the endoplasmic
reticulum and activation of protein kinase C (PKC). M2 and M4 are coupled to G i thus
inhibiting adenylyl cyclase. The G i β/γ-subunits activate GIRK channels (inwardly rectifying K + -channels) and induce hyperpolarization. M2 is localized at the heart and is important for control of heartbeat and rhythm. In pacemaker cells the “funny current” or
pacemaker current, which is a result of the opening of “hyperpolarization-activated cyclic
nucleotide-gated cation channels” (HCN), is inhibited by the acetylcholine
signalling- induced decrease in cAMP. The opening of GIRK channels makes it harder for
the pacemaker cells to be depolarized. Physiologically this is important for maintenance
of the regular heartbeat (Kruse et al. 2014); see . Fig. 5.2.
Many synthetic compounds have been developed to block MAchR signalling, e.g. benztropine (trade name Cogentin), which is used to treat symptoms of Parkinson’s disease,
and so-called long-acting muscarinic receptor antagonists LAMAs like aclidinium, glyChapter 5 · GPCRs as Targets for Plant-Derived Drugs