a. Animals are active organisms, and have the following systems to guide their actions:

b. Superimposed over these systems are control and communication systems.

c. Every organism collects and responds to critical information and also must continually monitor its internal environment.

d. Animals maintain homeostasis by adjusting enzyme systems, by turning genes on and off, by changing the concentrations of substances, and by sometimes altering behaviors.

e. Regulation entails feedback loops using sensor cells that monitor conditions and effector cells that change conditions (Figure 41.1).

f. Sensors detect light, heat, mechanical pressures, and concentrations, and effectors are muscles and glands that respond to these senses.

g. Two systems of integrators or communicators–an endocrine (or hormonal) system and a nervous system–are active with the sensor and effector systems.

h. The immune system provides sensors of another kind.

a. In the early 1900s, W. M. Bayliss and E. H. Starling analyzed the pancreatic and digestive systems of dogs.

b. A series of experiments showed that the pancreas is stimulated to secrete fluids by a factor that is released into the blood by cells lining the intestine.

c. Bayliss and Starling called the stimulating chemical secretin and realized that only specific target cells of the pancreas would react to its presence in the blood, though many other body cells were exposed to the secretin.

d. Bayliss and Starling coined the term hormone (Greek, hormaein = "to impel") to describe material, such as their secretin, that carries a signal from one set of cells to another.

e. A hormone is a substance secreted into the circulation by certain cells that produces a response in certain other cells, the target cells.

f. Hormonal communications entail two specificities: The hormone itself only affects target cells that are able to recognize and receive it, and the target cell has its own characteristic activity, so one hormone may stimulate two different cells to perform quite different processes.

g. A hormone could be virtually any distinctive molecule, but animal hormones fall into four categories:

a. Insulin and glucagon maintain a constant glucose concentration in the blood of vertebrates and nicely illustrate the action of peptide hormones.

b. Glucose ("blood sugar"), the usual source of energy for all cells, must be kept at constant levels in the human bloodstream.

c. Hypoglycemia results from too little glucose in the blood, and causes weakness, dizziness, sweating, and possible loss of consciousness.

d. Hyperglycemia results from too much glucose in the blood, and can eventually lead to impaired circulation, damage to the eyes, kidneys, and other organs, and often death.

e. Most of the glucose eaten by vertebrates is converted to glycogen stored in liver, muscle, and adipose cells, and is released gradually into the bloodstream.

f. A vertebrate's blood glucose level is kept constant by a negative feedback system involving glucagon and insulin.

g. Insulin and glucagon are synthesized and stored in the pancreas, an organ made of both exocrine glands and endocrine glands (Figure 41.2).

h. Exocrine glands are pockets of specialized epithelial cells that produce materials such as digestive enzymes, sweat, tears, and oils that are released through ducts to the outside of the body or the intestinal system.

i. Endocrine glands secrete hormones and release their secretions into the interstitial fluid, from where they pass into the bloodstream.

j. The islets of Langerhans make up the endocrine regions of the pancreas, where insulin and glucagon are synthesized and plasma glucose concentrations are monitored by specialized cells (Figure 41.3).

k. In the plasma membranes of muscle and liver cells, target cells for glucagon or insulin have specific membrane receptor proteins that are capable of binding one hormone or the other and thus triggering either the metabolism or storage of glucose (Figure 41.4).

a. Signal ligands are hormones and other molecules that carry a chemical message.

b. Signal ligand receptors, all of which are proteins with specific binding sites, only act in one of four ways, as shown in Figure 41.5.

c. G-protein-linked receptors are described in detail in Section 11.8.

d. The link between a small signal and a large effect is a reaction cascade, a kind of biological amplifier that involves a series of inactive molecules that are activated in succession.

e. The cascade initiated by glucagon employs a series of protein kinases that activate one another and cause a breakdown of glycogen to glucose (Figure 41.6).

f. In other cascades, the inactive proteins are proenzymes that have extra peptides blocking their active sites and are activated by removal of these peptides.

g. Catalytic receptors are inactive membrane enzymes that are activated when a ligand binds to them; they usually also cause cascades.

h. Channel-linked receptors open ion-channel ligand-gated proteins, which allow specific ions to flow through membranes.

i. Lipid-soluble hormone receptors are intracellular protein receptors that regulate specific sets of genes.

a. Neighboring cells in an organism communicate via gap junctions or via molecules bound to their surfaces.

b. Cells that are not in direct contact use secreted signal ligand in one of three types of communication (Figure 41.7):

c. Growth factors (Section 20.8) and functionally related proteins called lymphokines are paracrine factors involved in the processes of inflammation and immunity (Chapter 48).

d. Nitric oxide is a recently discovered paracrine factor called a local chemical mediator; it is also a neurotransmitter.

e. The prostaglandins are fatty acid derivatives that act as local chemical mediators in many organs and which stimulate either contraction or relaxation of smooth muscles such as those found in the uterus, oviducts, or blood vessels.

a. The central nervous system (CNS) includes the brain and the spinal cord, which runs through the vertebral column.

b. The peripheral nervous system (PNS) is made of nerves, paired right and left, that connect the CNS to effectors and receptors in the rest of the body (Figure 41.9).

c. The general terms "afferent," meaning toward, and "efferent," meaning away from, describe neurons (nerve cells) in reference to the CNS.

d. Afferent neurons carry messages from sense organs toward the CNS and are therefore also called sensory neurons.

e. Efferent neurons carry messages from the CNS to the body's effectors, thus are also called motor neurons.

f. Twelve pairs of cranial nerves emerge from centers in the brain, and a pair of spinal nerves generally emerge at each level of the spinal cord between the vertebrae.

g. The motor portion of the nervous system has two parts:

h. Figure 41.9 diagrams the relationships between the various parts of the nervous system.

a. A nervous system gathers information from many internal and external points, processes and integrates the information, and sends instructions for action to effector organs.

b. The nervous system converts all incoming information into nerve impulses, waves of electrochemical change that travel rapidly in the membranes of neurons.

c. External signals must be transduced into this language, and signals carried to effector organs must be transduced into their actions.

d. Nervous tissue is made of several types of cells.

e. Nerve signals are encoded by changing the rate at which a neuron "fires," or sends impulses.

f. The cell bodies of neurons with similar functions cluster together (Figure 41.11) into what is termed either a nucleus (inside the CNS) or a ganglion (inside the PNS).

g. A bundle of axons and dendrites bound together is called a tract if it is within the CNS, and is called a nerve if it is outside the CNS.

h. Information at a synapse passes only one way: from the presynaptic cell (a neuron) across the synaptic cleft to the postsynaptic cell, which could be another neuron or a gland or muscle cell (Figure 41.12).

i. Vesicles stimulated in the presynaptic cell ending release ligands into the synaptic cleft; these ligands bind to receptors of ligand-gated channels on the postsynaptic plasma membrane, stimulating a response.

a. A classic reflex arc nicely illustrates the general operation of a nervous system (Figure 41.13).

b. A sensory neuron runs from a receptor (e.g. in the hand) into the spinal cord, synapses with a short interneuron that, in turn, synapses with a motor neuron leading back to an effector (e.g. a group of arm muscles).

c. Reflex actions (e.g. pulling your hand away from a hot object) happen quickly, unconsciously, spontaneously, and in a fairly stereotyped way in response to particular stimuli.

d. The neurons in a reflex arc are modified by other fibers that determine the extent and direction of the reflex action.

e. The spinal cord and brain are both involved in a complicated analysis and response to stimuli that cause reflex actions, long after the reflex action has occurred.

f. The CNS contains a decision-making apparatus made of lower and higher brain centers that process information and integrate it with stored information from previous experiences.

a. Nerve impulses are changes in voltage or electrical potential, a measure of the force that tends to make ions or electrons move from one place to another.

b. Potential (e.g. chemical potential) is a general term for a force that can do work.

c. A voltage exists wherever ions or electrons tend to move from place to place; the magnitude of the voltage is a measure of the potential for work.

d. Much of our knowledge regarding neurons has come from work on the giant axons of squid (Figure 41.14), as described in the following procedure:

e. All cells have a membrane potential; their magnitudes vary from one cell type to another.

f. The conductance of a membrane is a measure of its permeability to ions.

g. The plasma membrane's conductance is about 30 times lower for inorganic ions than it is for K+ and Na+ ions.

h. In a squid axon, the internal concentration of K+ ions is 410 mM, and the external concentration is only 22 mM, so that K+ ions tend to diffuse out of the axoplasm.

i. As ions diffuse outward, they create a charge imbalance, a voltage, with an excess of positive charge outside and negative charge inside.

j. Potassium ions will only diffuse outward until their electrical potential just balances their chemical potential, and they come to an equilibrium distribution.

k. This equilibrium occurs when only a small fraction of K+ ions are outside, and there is then an electrochemical potential across the membrane, an unequal distribution of ions that creates the resting potential of -70mV, with the inside negative.

l. Oscilloscope readings of membrane potential range from -100 mV to around +6- mV; the voltage is lower or higher, increasing or decreasing as it changes along this scale.

a. If the squid axon is stimulated with a brief electric shock, the oscilloscope shows a sudden rise to +50 mV, indicating the inside of the axon is now positive with respect to the outside.

b. This transient change in potential is an action potential, also called a "spike" because of its appearance on the oscilloscope screen.

c. A gradual increase in membrane voltage has no effect until the voltage reaches a threshold, around -50 mV, where the axon suddenly responds with an action potential.

d. An axon potential is thus an all-or-none event.

e. The axon membrane contains voltage-gated channels for Na+ and K+ ions, transmembrane proteins that open their ion gates in response to the membrane voltage.

f. The Na+ channels go through a positive feedback loop, the Hodgkin cycle (Figure 41.16); as membrane voltage increases, Na+ ions move inward and open more and more channels, allowing more ions to enter, and causing the membrane to react explosively.

g. The Na+ channels then close, making the membrane again impermeable to Na+ ions, while voltage-gated K+ channels open, and the outward flow of K+ ions creates the falling phase of the action potential.

h. The overall composition of the cytosol actually changes little during an action potential, as relatively few ions move across the membrane to create this local potential charge.

a. An action potential generated at one point on an axon becomes a nerve impulse that moves along the axon (Figure 41.17), as Na+ ions entering in one region of the axon repel other positive ions, which move to the side and raise the neighboring voltage, creating an action potential in that area, and so on.

b. The action potential phenomenon accounts for two important properties of a nerve impulse:

c. If the voltage across an axon membrane is raised above the normal resting value, the axon responds with a series of nerve impulses whose frequency increases as the voltage is set higher (Figure 41.18).

a. Neurons, the cells that carry nerve signals, comprise only about 10 percent of mammalian nervous system cells.

b. The rest of the nervous system consists of several kinds of glial cells, or neuroglia, which nourish, protect, and support neurons.

c. In the vertebrate peripheral nervous system, Schwann cells wrap around neurons to make a myelin sheath, which insulates one axon from another and keeps ions from moving across the axon membrane.

d. At small gaps between the Schwann cells, called the nodes of Ranvier, Na+ and K+ ions can move across the axon membrane through their channels.

e. A nerve impulse skips from node to node in saltatory conduction, which is faster than continuous conduction in an unmyelinated axon (Figure 41.19).

f. The velocity of a nerve impulse increases with myelination and also with the diameter of the axon.

a. Nervous system impulses are triggered by synaptic inputs from other neurons or from receptor cells.

b. The dendrites and soma of a typical neuron are studded with axon endings from other neurons that each provide input (Figure 41.20).

c. Every neuron is either inhibitory or excitatory: it either decreases or increases the activity of the postsynaptic cells to which it is connected.

d. Each neuron generally produces a single kind of neurotransmitter at its synapses, and both the neurotransmitter and the synapse are either excitatory or inhibitory.

e. The balance of the excitatory and inhibitory signals on any neuron at a given time determines whether the neuron will fire.

f. At an excitatory synapse, the neurotransmitter creates a local increase in the membrane potential, an excitatory postsynaptic potential (EPSP).

g. At an inhibitory synapse, the neurotransmitter stimulates a local decrease, an inhibitory postsynaptic potential (IPSP).

h. EPSPs and IPSPs are graded potentials, not all-or-none, since the dendrites and soma membranes are ligand-gated, not voltage-gated, and they can add to, or subtract from, each other if they are generated close together (Figure 41.21).

i. The magnitude of a potential is proportional to the strength of the incoming stimulus, which is probably determined by the amount of neurotransmitter released.

j. Potentials are conducted decrementally; they diminish as they spread across the membrane.

k. A neuron is thus like an adding machine: it sums up the EPSPs and IPSPs generated across its membrane, and triggers a nerve impulse if the total potential is above the threshold.

l. An inhibitory cell may form a negative feedback loop in a circuit, so once a cell has transmitted a signal, it is inhibited and will not fire again for a time (Figure 41.22).

m. Inhibitory neurons can also be used for collateral inhibition (Figure 41.22), as those in the middle of a group of parallel neurons may inhibit the more peripheral ones.

n. Many neurons (e.g. those essential for breathing and heartbeat) fire spontaneously and continually, as they apparently allow Na+ ions to continually leak through their membranes until they fire, reset, and repeat the process.

a. The pituitary gland, or hypophysis, is a tiny organ situated just below the hypothalamus, where it is well protected by bone (Figure 42.10).

b. The pituitary and hypothalamus together form a center of regulation in vertebrates that controls most other endocrine glands.

c. Hypothalamus neurons sense factors such as temperature and ionic concentrations in the interstitial fluid, and they regulate these factors with nervous signals and signals to the pituitary.

d. The posterior pituitary is essentially an extension of the hypothalamus (Figure 41.23) and it secretes two small peptide hormones: oxytocin, which accelerates labor and childbirth, and vasopressin, which helps regulate blood pressure and the body's water content.

e. These hormones are synthesized and packaged into vesicles in neurons called neurosecretory cells, which lie in the hypothalamus.

f. Neurosecretory cells are thus specialized neurons, which store signal ligands in terminal vesicles and release them upon stimulation.

g. The anterior pituitary gland (adenohypophysis) develops as an outgrowth of the embryonic mouth, and produces seven peptide hormones that regulate either cellular activity or reproduction (Figure 41.24).

h. Each specialized pituitary cell synthesizes one of these hormones under the control of equally specialized cells that produce releasing hormones.

i. Releasing hormones control the release of anterior-pituitary hormones, which may, in turn, stimulate the release of hormones by still other endocrine glands, thus providing several points of regulation.

j. Figure 41.25 illustrates thyroid hormone control system; Figure 41.26 shows a person with a goiter, an abnormal growth of the thyroid gland.

a. A vertebrate's relaxed behavioral state is maintained by the parasympathetic division of the ANS (Figure 41.27), which keeps the eyes set for close vision, the heart pumping slowly, and the intestinal tract calmly digesting food.

b. The sympathetic division of the ANS takes over when an animal is alarmed, causing the eyes to adjust for more light and focus on potential danger in the distance, the heart to pump faster, the air passages to dilate, and digestive activities to stop.

c. The ANS has a third enteric nervous system, which controls gastrointestinal tract activities.

d. Most organs in the body can be stimulated to carry out opposite activities by the two classical division of the ANS, thus the nervous system can carry different messages by having neurons that produce different neurotransmitters.

e. Adrenergic neurons, for instance, produce the neurotransmitter noradrenaline (norepinephrine), and cholinergic neurons produce acetylcholine.

f. The somatic and parasympathetic systems are built entirely of cholinergic neurons and the sympathetic system is built of both cholinergic and adrenergic neurons (Figure 41.28).

g. These two signal ligands produce opposite autonomic effects on each organ, but whether each ligand excites or inhibits depends on the organ's signal-transduction mechanism.

h. A signal ligand may have different effects because it binds to different receptors, the classic example being the binding of epinephrine to either alpha-adrenergic or ß-adrenergic receptors, which are distinguished experimentally by their ability to bind drugs.

i. The close connections between the nervous system and certain hormones can be illustrated by sympathetic neurons that run directly from the CNS to the adrenal glands.

j. Adrenal medulla and sympathetic system work together, as a sympathoadrenal system.