Human Physiology Chapter 5: Chemical Messengers

Intercellular Communication

• communication between cells nearby or at a distance

  • direct

  • indirect

Intercellular Communication Process

• 2 or more cells sharing/communication of info and response to the communicated info

Direct Intercellular Communication

• direct communication: gap junctions

• involves: connexins and connexons

• communicated info: ions and small molecules

• ex: heart muscle, smooth muscle that controls intestines and blood vessels, between glands, neurons and retina

• response: functions to synchronize cells, electrically coupling cells

Indirect Intercellular Communication

• transport of chemical messenger through the interstitial fluid

• strength of target cell response depends on

  • concentration of the messenger near the target cell

  • number of receptors available to bind the messenger

  • sensitivity of the receptors for the messenger

  • identity of the responding receptor

Functional Classes of Chemical Messengers

• paracrine

• autocrine

• neurotransmitters

• hormones

Paracrine Based Chemical Messenger

• molecules diffuse through extracellular fluid to reach target molecule

• target cell is nearby the secreting cell

• autocrine molecules are secreted by and act on the same cell

Example of Paracrine Messenger

• growth factors that control cell growth and differentiation

• clotting factors

• cytokines with a role in immune defense

  

Neurotransmitters

• released by neurons (presynaptic cell) at the axon terminal

• diffusion across the synapse

• received by a neuron, gland cell, or muscle (postsynaptic cells), cells associated with the axon terminal

• synaptic signaling

Example of Neurotransmitters

• acetylcholine, impacts skeletal muscles

Hormones

• synthesized and released by endocrine cells into interstitial fluid and move rom here into the blood

• transported through the blood stream to target cells

• only cells with a receptor for the hormone can respond

Example of Hormones

• insulin produced by B-cells in the pancreas

• it impacts insulin receptor containing cells

Neurohormones

• secreted by specialized hormones

  • vasopressin (antidiuretic hormone) secreted by neurosecretory cells in the posterior pituitary, travels in blood to the kidney

Functional Classification of Chemical Messengers

Chemical Classification of Messengers

major characteristic off chemical messengers

• lipophilic

• lipophobic

• amino acid messengers

Lipophilic

• lipid soluble; hydrophobic

• cross a membrane environment, not freely transported in the plasma

Lipophobic

• water soluble; hydrophilic

• must be transported across a membrane environment, transported in plasma

Amino Acid Messengers

• lipophobic/hydrophilic

• neurotransmitters

  • glutamate, aspartate, glycine, gamma-aminobutyric acid (GABA)

• synthesized in the cytosol of neurons using intermediates from the oxidation o glucose

• stored in membrane bound vesicles until exocytosis

Amine Messengers

• primarily lipophobic/hydrophilic

• derived from amino acids

• neurotransmitters

  • dopamine, norepinephrine, serotonin, and histamine

• hormone

  • epinephrine, thyroid hormone

Catecholamines

• synthesized in secretory cells from tyrosine

Serotonin

• synthesized from tryptophan in the cytosol

Histamine

• synthesized from histidine in the cytosol

Peptide/Protein Messengers

• 2-100 amino acids

• lipophobic/hydrophilic

• synthesized on the RER

• cleavage and transport to Golgi

• packaged into secretory vesicle

• final cleavage can occur in the golgi or secretory vesicle

Steroid Messengers

• lipophilic/hydrophobic

• derived from cholesterol

• hormones: estradiol

• synthesized by enzymes located in the SER and mitochondria

• can not be store, synthesized on demand

• difffuses into intersitial fluid

Eicosanoid Messengers

• lipophilic/hydrophobic

• derived from phospholipid/arachinidonic acid

• paracrine

• utilizes enzymes found in the ER and mitochondria

• can not be stored, synthesized on demand

• diffuses into interstitial fluid

Chemical Classification off Messengers

Hydrophilic Messengers Transport

• freely soluble in the interstitial fluid/blood

Paracrine and Neurotransmitters Messengers Transport

• hydrophilic messenger

• release near the target cell; diffuses to target

• degradation in the interstitial fluid reduces activity to a local

Hormones, Peptides, and Amines Messengers Transport

• hydrophilic messenger

• dispersal through blood stream

• some amines (catecholamines) are bound to carrier proteins

Hydrophobic Messenger Transport

• not very soluble in the interstitial fluid/blood

• bound to carrier proteins

  • carrier proteins may be specific to the messenger or general (albumin)

  • steroids, thyroid hormones

• 99 percent of hydrophobic messengers are bound to a carrier proteins for transport

• free hormone can leave plasma and bind to receptors on target cells

Receptors

• located in plasma membrane, cytosol, or nucleus of the target cell

• a single chemical messenger can bind to multiple different receptors

• a single cell has multiple receptors and can respond to multiple different chemical messengers

  • skeletal muslce have receptors for acetylcholine and insulin

Chemical Messenger

• receptor interactions are either

  • specific

  • transient

  • reversible

Factors That Influence Target Cell Response

• concentration of the messenger

• number of receptors

• affinity of the receptor for the chemical messenger

Receptor Agonists

• ligands that bind to receptors and induces a response

Receptor Antagonists

• ligands that bind to receptors and block a response, competes with agonists

Target Cell Response: Lipophilic Messengers

• freely enters the cytosol

• binds to cytoplasmic/nuclear receptors and the receptor binds to DNA and activates transcription

• mRNA translated into protein

• long activation process

• persist past the presence of the messenger

• steroid receptors found in the cytoplams and nucleus

• thyroid hormone receptors found in nucleus

Receptor For Lipophobic Messengers (Channel Linked)

• chemical messenger binding promotes opening of an ion channel

• the influx of ions alters the membrane potential of target cell and ions can associate with intracellular proteins and alter their activity

• target cell response is fast and continues as long as the chemical messenger is bound to its receptor

• ex; acetylcholine binding to nicotinic cholinergic receptor on skeletal muscle leads to influx of sodium ions

Receptor For Lipophobic Messengers (Enzyme-Linked Receptor)

• messenger binding to an enzyme-linked receptor induces a change in conformation

• autophosphorylation of the cytosolic domain of the receptor activates its kinase activity

• activated receptor targets intracellular proteins for phosphorylation, triggering an intracellular response

Receptor For Lipophobic Messengers (G-Protein Linked)

• chemical messenger binding activates an associated heterotrimeric G-protein

• the alpha-subunit, with GTP bound, activates an effector molecule (channel or enzyme)

• GTP hydrolysis by the alpha-subunit reverts it back into its inactivate state

Comparison of Liphophobic and Lipophilic Messenger