Responses to Cholinergic Stimulation

All somatic motor neurons, all preganglionic neurons (sympathetic and parasympathetic), and most postganglionic parasym-pathetic neurons are cholinergic—they release acetylcholine (ACh) as a neurotransmitter. The effects of ACh released by somatic motor neurons, and by preganglionic autonomic neurons, are always excitatory. The effects of ACh released by post-ganglionic parasympathetic axons are usually excitatory, but in some cases they are inhibitory. For example, the cholinergic effect of the postganglionic parasympathetic axons innervating the heart (a part of the vagus nerve) slows the heart rate. It is useful to remember that, in general, the effects of parasympathetic innervation are opposite to the effects of sympathetic innervation.

The effects of ACh in an organ depend on the nature of the cholinergic receptor (fig. 9.11). As may be recalled from chapter 7, there are two types of cholinergic receptors—nicotinic and mus-

Chapter Nine carinic. Nicotine (derived from the tobacco plant), as well as ACh, stimulates the nicotinic ACh receptors. These are located in the neuromuscular junction of skeletal muscle fibers and in the autonomic ganglia. Nicotinic receptors are thus stimulated by ACh released by somatic motor neurons and by pre-ganglionic autonomic neurons. Muscarine (derived from some poisonous mushrooms), as well as ACh, stimulates the ACh receptors in the visceral organs. Muscarinic receptors are thus stimulated by ACh released by postganglionic parasympathetic axons to produce the parasympathetic effects. Nicotinic and muscarinic receptors are further distinguished by the action of the drugs curare (tubocurarine), which specifically blocks the nicotinic ACh receptors, and atropine (or belladonna), which specifically blocks the muscarinic ACh receptors.

As described in chapter 7, the nicotinic ACh receptors are ligand-gated ion channels. That is, binding to ACh causes the ion channel to open within the receptor protein. This allows Na+ to diffuse inward, causing depolarization. As a result, nicotinic ACh receptors are always excitatory. In contrast, muscarinic ACh receptors are coupled to G-proteins, which can then close or open different membrane channels and activate different membrane enzymes. As a result, their effects can be either excitatory or inhibitory (fig. 9.11).

Scientists have identified five different subtypes of mus-carinic receptors (Mj through M5; table 9.6). Some of these cause contraction of smooth muscles and secretion of glands, while others cause the inhibition that results in a slowing of the heart rate. These actions are mediated by second-messenger systems that will be discussed in more detail in conjunction with hormone action in chapter 11.

Clinical Investigation Clues

Remember that Cathy developed a headache, dry mouth, and dilated pupils following the use of various drugs in the frog heart lab.

■ Which drug likely produced these effects in Cathy?

■ How did the drug have these effects?

The muscarinic effects of ACh are specifically inhibited by the drug atropine, derived from the deadly nightshade plant (Atropa belladonna). Indeed, extracts of this plant were used by women during the Middle Ages to dilate their pupils (atropine inhibits parasympathetic stimulation of the iris). This was thought to enhance their beauty (in Italian, bella = beautiful, donna = woman). Atropine is used clinically today to dilate pupils during eye examinations, to reduce secretions of the respiratory tract prior to general anesthesia, to inhibit spasmodic contractions of the lower digestive tract, and to inhibit stomach acid secretion in a person with gastritis.

The Autonomic Nervous System 233

Nicotinic ACh receptors

Muscarinic ACh receptors

Postsynaptic membrane of

• All autonomic ganglia

• All neuromuscular junctions

• Some CNS pathways

• Produces parasympathetic nerve effects in the heart, smooth muscles, and glands

• G-protein-coupled receptors (receptors influence ion channels by means of G-proteins)

IMMMM IIMMIIM

IMMMM IIMMIIM

nnuMiwi

, i, j Ligand-gated channels (ion channels are part of receptor)

Depolarization nnuMiwi

Depolarization

Excitation

, i, j Ligand-gated channels (ion channels are part of receptor)

Hyperpolarization

Hyperpolarization

(K+ channels opened)

Inhibition

Produces slower heart rate

-ACh

-ACh

Depolarization

(K+ channels closed)

Excitation

Causes smooth muscles of the digestive tract to contract

Figure 9.11 Comparison of nicotinic and muscarinic acetylcholine receptors. Nicotinic receptors are ligand-gated, meaning that the ion channel (which runs through the receptor) is opened by binding to the neurotransmitter molecule (the ligand). The muscarinic ACh receptors are G-protein coupled receptors, meaning that the binding of ACh to its receptor indirectly opens or closes ion channels through the action of G-proteins.

Figure 9.11 Comparison of nicotinic and muscarinic acetylcholine receptors. Nicotinic receptors are ligand-gated, meaning that the ion channel (which runs through the receptor) is opened by binding to the neurotransmitter molecule (the ligand). The muscarinic ACh receptors are G-protein coupled receptors, meaning that the binding of ACh to its receptor indirectly opens or closes ion channels through the action of G-proteins.

Table 9.6

Receptor

Cholinergic Receptors and Responses to Acetylcholine

Tissue Response Mechanisms

Nicotinic

Skeletal muscle

Depolarization, producing action potentials and muscle contraction

ACh opens cation channel in receptor

Nicotinic

Autonomic ganglia

Depolarization, causing activation of postganglionic neurons

ACh opens cation channel in receptor

Muscarinic (M3, Muscarinic (M2)

) Smooth muscle, glands Heart

Depolarization and contraction of smooth muscle, secretion of glands Hyperpolarization, slowing rate of spontaneous depolarization

ACh activates G-protein coupled receptor, opening Ca2+ channels and increasing cytosolic Ca2+ ACh activates G-protein coupled receptor, opening channels for K+

Source: Simplified from table 6-2, p. 119 of Goodman and Gilman's The Pharmacological Basis of Therapeutics. Ninth edition. J.E. Hardman et al., eds. 1996. McGraw-Hill.

Source: Simplified from table 6-2, p. 119 of Goodman and Gilman's The Pharmacological Basis of Therapeutics. Ninth edition. J.E. Hardman et al., eds. 1996. McGraw-Hill.

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Responses

  • Mat
    Are there nicotinic ach receptors on smooth muscle?
    8 years ago
  • zewdi temesgen
    What is nicotinic response mechanism poisoning?
    7 years ago
  • Assunta Beneventi
    Is Atropine a excitatory or inhibitory drug?
    7 years ago
  • arwen
    Which receptor nicotinic or muscarinic produces the fastest response?
    7 years ago

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