The receptor for acetylcholine in skeletal muscle is called nicotinic because nicotine can imitate the action of this neurotransmitter. On the other hand, the receptor for acetylcholine in cardiac muscle is called muscarinic because muscarine, a compound derived from the Amanita muscaria mushroom, can replicate this effect.

Cell-to-cell communication is facilitated by five fundamental mechanisms: contact-dependent, paracrine, autocrine, synaptic, and endocrine signaling. These mechanisms are thoroughly explained in the text.

Nuclear receptors are influenced by extracellular ligands such as GABA, ACh (muscle), ATP, and glutamate (specifically NMDA). Intracellular ligands include neurotransmitters (ACh), peptides (PTH, oxytocin), odorants, cytokines, and lipids. Other ligands that affect nuclear receptors are ANP, TGF-β, insulin, EGF, interleukin-6, erythropoietin, and various steroid hormones.

Membrane currents are affected by different ions, such as Cl-, Na+, K+, and Ca++. Additionally, beta-gamma subunits activate ion channels, while alpha subunits activate enzymes such as cyclases (which generate cAMP and cGMP), phospholipases (which generate InsP3, diacylglycerol, and arachidonic acid and its metabolites), monomeric G proteins, receptor guanylyl cyclase, receptor serine/threonine kinase, and receptor tyrosine kinase. Receptors also bind to regulatory sequences in DNA to either increase or decrease gene transcription.

All signaling molecules bind to specific receptors that act as signal transducers, converting ligand-receptor binding events into intracellular signals that affect cellular function. Receptors can be categorized into four main classes based on their structure and mechanism of action: ligand-gated ion channels, G protein-coupled receptors (GPCRs), enzyme-linked receptors, and nuclear receptors.

Neurotransmitters bind to receptors and can either open or close ion channels, leading to changes in the ionic permeability of the plasma membrane and alterations in the membrane potential. GPCRs regulate the activity of other proteins, such as enzymes and ion channels, through the interaction between the receptor and the target protein. This interaction is mediated by heterotrimeric G proteins, which consist of alpha, beta, and gamma subunits. Stimulation of G proteins by ligand-bound receptors either activates or inhibits downstream target proteins involved in signaling pathways or alters membrane ion permeability if the target protein is an ion channel.
aThe acetylcholine receptor in skeletal muscle is termed nicotinic because nicotine can mimic this action of the neurotransmitter. In contrast, the acetylcholine receptor in cardiac muscle is termed muscarinic because this effect is mimicked by muscarine, an alkaloid derived from the mushroom
Amanita muscaria.
• Fig. 3.3 Cell-to-cell communication is mediated by five basic mechanisms: contact-dependent (A), paracrine (B), autocrine (C), synaptic (D), and endocrine signaling (E). These mechanisms are described in detail in the text. (Redrawn from Alberts B, et al: Molecular Biology of the Cell. 6th ed. New York: Garland Science; 2015.)
CHAPTER 3 Signal Transduction, Membrane Receptors, Second Messengers, and Regulation of Gene Expression
Nuclear receptors Extracellular ligand:
GABA ACh (muscle) ATP Glutamate: NMDA
Intracellular ligand:
Neurotransmitters (ACh) Peptides (PTH, oxytocin) Odorants Cytokines, lipids
ANP TGF-β Insulin, EGF Interleukin-6, erythropoietin Steroid hormones:
Miscellaneous hormones:
Membrane currents: Cl− Na+ , K+ , Ca++ Ca++ , Na+ , K+ Na+ , K+ , Ca++
K+ Na+ , K+ Ca++ βγ Subunits activate ion channels α Subunit activates enzymes:
Cyclases that generate cAMP, cGMP, phospholipases that generate InsP3 and diacylglycerol, and phospholipases that generate arachidonic acid and its metabolites.
Monomeric G proteins Receptor guanylyl cyclase Receptor serine/threonine kinase Receptor tyrosine kinase Tyrosine kinase–associated receptor Bind to regulatory sequences in DNA and increase or
Bind to regulatory sequences in DNA and increase or decrease gene transcription
ACh, acetylcholine; ANP, atrial natriuretic peptide; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate; EGF, epidermal growth factor; GABA, gamma-aminobutyric acid; InsP3, inositol 1,4,5-triphosphate; NMDA, N-methyl-D-aspartate; PTH, parathyroid hormone; TGF, transforming growth factor.
All signaling molecules bind to specific receptors that act as signal transducers, thereby converting a ligand-receptor binding event into intracellular signals that affect cellular function. Receptors can be divided into four basic classes on the basis of their structure and mechanism of action: (1) ligand-gated ion channels, (2) G protein–coupled receptors (GPCRs), (3) enzyme-linked receptors, and (4) nuclear receptors (
Table 3.1
Figs. 3.4 3.5).
Fig. 3.4A). Neurotransmitters bind to receptors and either open or close ion channels, thereby changing the ionic permeability of the plasma membrane and altering the membrane potential. For examples and more details, see
GPCRs regulate the activity of other proteins, such as enzymes and ion channels (see
Fig. 3.4B ). In the example in
Fig. 3.4B , the interaction between the receptor and the target protein is mediated by heterotrimeric G proteins, which are composed of α, β, and γ subunits. Stimulation of G proteins by ligand-bound receptors activates or inhibits downstream target proteins that regulate signaling pathways if the target protein is an enzyme or changes membrane ion permeability if the target protein is an ion channel.