Physiology 31 Lecture Chapter 6 – Communication, Integration, and Homeostasis I. Overview A. Cell-to-Cell Communication B. Signal Pathways C. Cell Membrane Receptors D. Novel Signal Molecules E. Modulation of Signal Pathways F. Control Pathways: Response & Feedback Loops II. Cell-to-Cell Communication A. The two basic methods of physiological communication (_________) are chemical and electrical 1. __________ signals are changes in a cell’s membrane potential (voltage) via the flow of ions, as occurs in nerve impulses 2. ____________ signals result from cells secreting chemicals (e.g., hormones and neurotransmitters) into the extracellular space and blood stream 3. Cells that receive electrical or chemical signals are _______ cells B. Four types of cell-to-cell communication are 1. ________ cytoplasmic transfer of signals through gap junctions 2. ____________-dependent signaling – surface molecules of one cell bind to surface molecules of another cell 3. _________ chemical communication by chemicals that diffuse through the extracellular fluid 4. Long ____________ communication via both electrical signals from nerve cells and chemical signals in the blood stream C. ______ Junctions transfer chemical and electrical signals 1. Gap junctions are protein ________ between adjacent cells 2. When open, gap junctions allow ______ and small molecules to diffuse from cell to cell 3. Gap junctions are found between many cells, including ________ and smooth muscle cells, lung and liver cells, and some neurons D. ____________-dependent signals require cell-to-cell contact 1. Direct cell-to-cell contact signaling occurs in the ___________ system, and during growth and development 2. Cell Adhesion Molecules (_____s) bind some cells together and participate in cell-tocell signaling E. Paracrines & Autocrines are _______ chemical signals distributed by diffusion 1. _______________ are chemicals (e.g., histamine) secreted into the interstitial fluid in the extracellular space, and diffuse to ________ target cells 2. _______________ are chemicals that act on the same cell that secreted the chemical F. Electrical signals, Horomones, & Neurohormones carry out long ______________ communication 1. Endocrine gland cells secrete chemical messengers called ____________ into the blood stream a. Hormones travel in the blood stream to their _________ cells 2 b. Target cells have specific ____________ for the hormones 2. The __________ system uses both chemical and electrical signals a. ____________ signals travel to the end of a neuron and trigger the release of a chemical signal (neurocrine) to a target cell b. Neuro________ may be 1) Neuro____________ – fast acting chemical secreted across a gap between the neuron and its target cell 2) Neuro___________ – slow acting paracrine or autocrine chemicals 3) Neuro___________ – chemicals secreted into the blood stream G. Cytokines act as both ________ and long-distance signals 1. ___________ are regulatory molecules produced by all nucleated cells; they control cell development, differentiation, and immune response 2. In development and differentiation, cytokines are autocrine or ___________ 3. In stress and inflammation, cytokines are transported through the ________ stream III. Signal Pathways A. All _________ pathways share these common features 1. A signal molecule (_________, or 1st messenger) binds to its receptor. 2. Ligand binding activates the __________ 3. The receptor activates intracellular signal molecules (____ ___________) 4. The last ___________ molecule in the pathway either a. ____________ a target protein to create a response, or b. Initiates _____________ of a target protein B. _____________ are located inside the cell or in the cell membrane 1. Target cell receptors are found in the __________, the cytosol, or in the cell __________ 2. Chemical ___________ molecules are either water soluble (lipophobic) or lipid soluble (lipophilic) a. ________ soluble signals (e.g., peptide hormones) bind to receptors on the target cell ___________ and trigger an intracellular response b. _________ soluble signals (e.g., steroid hormones) usually diffuse through the target cell membrane and bind to cytoplasmic or _________ receptors 1) Receptor activation often turns on or off a _______ that directs protein synthesis C. Membrane ____________ facilitate signal transduction 1. Signal ___________ is the transmission of information from one side of the membrane to another via membrane proteins 2. Signal transduction ___________ use membrane proteins and intracellular 2nd messengers to produce an intracellular response a. A signal molecule binds to and activates a membrane ________ b. Some pathways activate protein ___________ that transfer a phosphate from _____ to a protein (i.e., phosphorylation) c. Other pathways activate amplifier __________ (e.g., adenylyl and guanylyl cyclase) that create 2nd messenger molecules (e.g., Ca2+, cAMP, cGMP) d. 2nd ___________, in turn can 1) Open or close ____ channels, which creates electrical signals 2) Increase intracellular ___________ levels 3 3) Change enzyme activity, especially in ___________ (phosphorylators) and ______________ (dephosphorylators) e. __________ modified by calcium binding and phosphorylation control 1) Metabolic ___________ 2) ________ proteins for muscle contraction and cytoskeletal movement 3) Proteins that regulate ______ activity and protein synthesis 4) Membrane ___________ and receptor proteins f. A signal transduction pathway is a _________ that begins when a stimulus (signal molecule) activates another molecule, which activates another, etc., until a product is eventually formed IV. Cell Membrane ___________ include receptor enzymes, G protein-linked, integrin, and ligand gated receptors A. Receptor-_______ have protein kinase or guanylyl cyclase activity 1. Receptor enzymes have receptors on the extracellular side of the membrane that activate __________ in the intracellular side 2. Receptor __________ (e.g., the insulin tyrosine kinase receptor) transfer phosphates from _____ to a protein 3. ____________ cyclase converts GTP to cyclic GMP (______), a second messenger 4. __________ for receptor enzymes include growth factors, cytokines, and the hormone insulin B. Most signal transduction uses ___ proteins 1. ___ ___________-coupled receptors span the cell membrane, and are linked to a G protein on the cytoplasmic side 2. Ligands that bind to these receptors include ___________, growth factors, and neurotransmitters 3. Ligand binding causes the G protein to exchange GDP for _____, thus activating the G protein 4. An ________ G protein can either a. Open an _____ channel in the membrane, or b. Alter __________ activity on the cytoplasmic side C. ___ ___________-coupled Adenylyl cyclase-cAMP is the signal transduction system for many ________ soluble hormones 1. __________ cyclase is a membrane enzyme that converts ATP to the 2nd messenger cyclic AMP (_____) 2. cAMP activates protein kinase A, which _________________ other proteins D. G protein-linked receptors also use _____-derived 2nd messengers 1. Ligand binding activates phospholipase C (___-__) 2. PL-C converts a membrane ___________ into 2 2nd messengers – diacylglycerol (DAG) and inositol triphosphate (IP3) a. _____ interacts in the membrane with protein kinase C, which ______________ cytosolic proteins b. ____ enters the cytoplasm and binds to a ________ channel on the ER, which opens the channel and allows Ca2+ to diffuse out 4 E. ____________ receptors transfer information from the ECM 1. Integrins are integral proteins that mediate blood clotting, wound repair, and other __________ functions 2. Ligands include antibodies and blood __________ molecules 3. Integrins attach to the _____________, and ligand binding can activate intracellular enzymes or alter cytoskeletal organization 4. Genetic defects in integrin proteins can result in defective WBCs and ____________ F. _________-________ ion channels initiate rapid intracellular responses via electrical impulses 1. These channels are found in _______ and muscle cell membranes 2. When a _________ (e.g., acetylcholine) binds, it opens or closes the _____ channel, altering the membrane’s electrical potential V. Novel Signal Molecules A. Calcium is an important intracellular ________ 1. ____________ enters the cytosol from a. _______cellular fluid via Ca2+ channels, or b. Intracellular compartments (e.g., ____), released by 2nd messengers, such as _____ 2. Once in the cytosol, Ca2+ affects cell activity by binding to a. ____________ protein, which alters enzyme activity or the open state of ion channels b. _________ proteins that alter movement of contractile proteins (e.g., troponin) or cytoskeletal proteins (e.g., microtubules) c. Other regulatory proteins that trigger ___________ of secretory vesicles (as in insulin secretion) d. _____ channels, to alter their open state (e.g., Ca2+ activated K+ channel of nerve cells) B. _________ are short-lived signal molecules 1. Nitric oxide (____) is an autocrine/paracrine gas formed from the amino acid _________ and oxygen a. NO diffuses into target cells and activates guanylyl cyclase, which in turn forms the 2nd messenger ______ b. In the brain, NO acts as a neuron___________ c. Blood vessel endothelial cells produce NO, which relaxes adjacent smooth muscle cells, causing vaso________ 2. Carbon monoxide (____) is produced in minute amounts, and has an action similar to NO. C. _______________ are important lipid paracrine signal molecules 1. Eicosanoids are all derived from _______________ acid, a 20 carbon fatty acid in the cell membrane 2. Two major __________ of eicosanoids are a. _____________, produced by lipoxygenase, contribute to asthmatic attacks and anaphylactic allergic reactions b. _____________, produced by cycloxygenase (COX), include prostaglandins and thromboxanes 1) _____________ are involved in inflammation, pain, and fever 2) _____________ stimulate vasoconstriction and blood clotting 5 3) Nonsteroidal anti-inflammatory drugs (__________s) prevent inflammation by inhibiting _______ enzymes 4) Steroidal anti-inflammatory drugs (______s) block arachidonic acid release VI. Modulation of Signal Pathways A. ____________ exhibit saturation, specificity, and competion 1. Like enzymes, each receptor binds to a __________ molecule (ligand) or related molecule. 2. The _____________ may be agonistic or antagonistic a. ___________ are ligands that activate receptors b. ______________ are competitors that block receptor activity 3. Different forms of a receptor (___________) can bind the same ligand and have different effects (e.g., epinephrine can bind to α & β adrenergic receptors) B. Up- and Down-Regulation of receptors enables cells to _________ cellular response 1. ________-regulation is a ____________ in a cell’s number of receptors or their binding affinity, often in response to _______ ligand concentrations (e.g., high insulin concentrations cause a down-regulation of insulin receptors in type II diabetes) 2. ___-regulation is an _________ in a cell’s number of receptors, often in response to _____ ligand concentrations, which increases the cell’s sensitivity to the ligand C. Cells have mechanisms for ___________ signal pathways, such as 1. ______________ the signal molecule, or 2. Breaking down the receptor-ligand _________ D. Pharmacologists investigate signaling ________________ to design drugs to treat disease. Examples of signal blockers are 1. ____________ channel blockers to treat high blood pressure 2. ____________s for treating estrogen-dependent cancers 3. _________ inhibitors that prevent the formation of inflammatory prostaglandins VIII. ____________ Pathways: Response and Feedback Loops A. _________________ responses have 3 components 1. A ______________ or change in a regulated variable 2. A cell or tissue that _____________ the stimulus and initiates a response 3. Cells or tissues that carry out the ___________ B. Homeostasis may be maintained by ________ or long-distance pathways 1. Local pathways include paracrine and ___________ responses 2. Long distance responses include __________ control pathways, which consist of ___________ loops that begin with a stimulus and end with a response a. ____________ or change is perceived by a b. _____________ (e.g., sensory neuron) that sends out an c. Input (___________) Signal to an d. _____________ center that evaluates the incoming signal, compares it to a ____________, then sends an e. Output (____________) signal (e.g., nerve impulse or hormone) to an f. ____________ (target cell or tissue) that carries out a g. ____________ to restore homeostasis 6 D. Negative and positive _________ loops modulate the response loop 1. ____________ feedback is when a change is sensed and a response is initiated to ______ the change and restore homeostasis 2. _____________ feedback is when a change is sensed and a response is sent to _____________ the change (e.g., hormonal control of uterine contractions during childbirth) E. Feed____________ control allows the body to anticipate change and start the response loop in anticipation of the change (e.g., salivation at the sight or smell of ______) F. Biological rhythms result from changes in the __________ 1. Reflexes that occur in a predictable manner, such as hormonal cycles, are called biological __________ 2. __________________ rhythms are those that coincide with light and dark cycles (e.g., blood pressure and body temperature) G. Control systems vary in their _______ and specificity 1. Nervous control is __________ and more specific than endocrine control, but is usually of ___________ duration 2. Endocrine control is ___________ and less specific, but is longer ____________ and is usually amplified 3. Many reflex pathways are combinations of ___________ and ____________ control mechanisms