• Composed of membrane proteins
• Link cytosol of two adjacent cells
• Particle movement between cells acts as signal
• Common in smooth and cardiac muscle
• Happens through connexons

• Paracrine
• Autocrine
• Neurotransporter
• Hormone

the secretory cell will release the signal and will be recognized by a nearby receptor on a target cell

ex. histamine

the secretory cell is also the target cell

ex. some interleukins

• chemical signal is produced by a nerve cell
• released into the ECF of the synaptic cleft
• target cell has a receptor that will receive the signal
• travels a short distance 
• NOTE: if a neuron is very long (can be up to 1 m) then neurotransmitters will be involved in long distance communication.
• ex. acetylcholine, glycine, serotonin

• produced by endocrine cells
• secreted into the blood via ISF
• ex. insulin, estrogen, thyroxin

• produced by neurons
• released into ISF, then blood
• ex. ADH, oxytocin

substances which have signaling function.

can be classified by function or by chemical properties

• Solubility
• Chemical Class

• General Properties
• not lipid soluble (is water soluble)
• does not easily cross the cell membrane, which may require pumps or channels
• has receptors on the cell membrane
• general action of target response is via enzyme activation
• membrane permeability changes
• Synthesis and Release
• synthesis is independent of demand
• stored in vesicles of source until needed
• release by exocytosis
• release rate determined by exocytosis

• General
• easily crosses the cell membrane
• the receptor location is within the target cell
• the general action of target response is via gene activation
• Synthesis and Release
• synthesized on demand
• immediate release from source
• release rate depends on synthesis

• lipophobic/hydrophilic
• synthesized within source (neuron)
• stored in vesicle until needed
• released by exocytosis
• target cell receptors on cell membrane
• only 4 amino acids function as messengers (all as neurotransmitters)
• Glutamate and Aspartate (both made from glucose)
• Glycine (made from 3-phosphoglycerate)
• GABA (made from glutamate)

• most are lipophobic/hydrophilic, except for thyroid hormones.
• produced in cytosol of source
• stored in vesicles of source
• release by exocytosis
• production depends upon enzymes of source
• target receptors on cell membrane
• made or derived from an amino acid; contain an amine group (-NH₂)
• List
• Catecholamines (tyrosine-derived): dopamine, norepinephrine, epinephrine.
• Thryoid Hormones (di-tyrosine-derived)
• Histamine (histadine-derived)
• Serotonin (tryptophan-derived) 

• The most abundant type of ligand.
• Lipophobic/Hydrophilic
• formed by cleaving larger proteins
• Prepropeptideàpropeptideàpeptideàprotein
• stored in secretory vesicles
• released by exocytosis
• Target receptors on the cell membrane.
• Made of chains of amino acids.
• Peptide Ligand is less than 50 amino acids.
• Protein Ligand is more than 50 amino acids.

• lipophilic/hydrophobic
• synthesized on demand
• derived from cholesterol molecule
• all steroid ligands are similar
• derived from cholesterol
• all function as hormones
• readily cross PM
• not water soluble; carrier protein in blood for many.

• lipophilic/hydrophobic
• synthesized on demand
• 2 major synthetic pathways (cyclooxygenase, lipoxygenase)
• have intracellular target receptors
• derived from arachidonic acid (a 20-carbon membrane phospholipid).
• Prostaglandins, Leukotrienes, Thromboxanes

the time it takes to decrease the concentration of a messenger in half.

when dissolved in plasma, there is a short half life.

when bound to a plasma protein, theres a long half life.

• the source and the target are close
• the ligand is quickly degraded
• paracrine, autocrine, neurotransmitter, most cytokines.

• source and target are at a distance
• lipophobic ligands dissolve in plasma
• lipophilic ligands bind to carrier protein.
• hormone, neurohormone, some cytokine.

• The process of producing a response in a target (how a chemical signal is translated).
• The messenger binds to a receptor, resulting in a cell response.
• Receptor Binding
• specific, brief, reversible
• affinity=strength of binding
• lipophobic ligands: cell membrane
• lipophilic ligands: within cell
• 1 messenger may have many receptor types or affinities.
• 1 target may have many types of receptors.

• Down-regulation of response is from: (1) decreased receptor numbers on target, (2) excess of messenger, (3) decreased sensitivity to messenger, (4) development of tolerance to messenger.
• Up-regulation of response is from: (1) receptor # increasing, (2) too little messenger, (3) sensitivity to messenger increased.
• Agonists and Antagonists

• Intracellular Mediated Responses
• Most lipophilic ligands (except thyroid hormones)
• receptors are in cytosol or nucleus
• cell response is via gene activation
• Membrane Receptor Mediated Response
• Target response: ion movement, enzyme phosphorylation
• Can be channel-linked, enzyme-linked, or G protein-linked receptors.

• Receptor and Channel are the same protein; the action is direct.
• The binding of the ligand causes the channel to open or close.
• The change in transport of ions through the channel causes the target response.

• Receptors and enzyme are the same protein.
• The ligand binding activates teh enzyme, action is direct.
• The activated enzyme causes the target response.
• Ex. tyrosine kinases, guanylate cyclases.

• G Proteins are regulatory proteins that link ECF messenger to ion channels, or amplifier enzymes.
• ECF messenger is the first messenger.

• The receptor/channel are different proteins, that are linked by G protein.
• binding of the ligand activates the G protein.
• The G protein activates the channel (the alpha segment will dissociate and pick up a phosphate from GTP, and will then move and attach to an ion channel, causing the channel to change shape).
• The change in ion transport through the channel causes the target response.

• the binding of the 1st messenger to receptor leads to the production of the 2nd messenger, which is intracellular and triggered by the first messenger activating G Protein.
• G Protein activates amplifier enzyme (Gi: inhibits, Gs: activates).
• Gs activates 2nd messenger production, for the purpose of signal amplification.
• ex. cAMP, Phosphatidylinositol

Signal Transduction and Amplification; small amounts of ligand can cause a huge response in the target, with each step recruiting more participants.

Can go from 1 to millions. 

• endocrine glands secrete hormones, which enter the blood.
• The blood spans the distance to the target.

• Nerve Cells can Transmit Signals
• Within neuron via long axons
• Between cells via the synapse
• Signals of axons=action potentials.
• Axons via action potentials span the distance to the target.

• Derived from epithelial tissue
• Primary Endocrine Organs' main function is to secrete hormones.
• Secondary Endocrine Organs secondary function is to secrete hormones.
• Includes hypothalamus and pituitary gland (master).
• Posterior pituitary secretes ADH and oxytocin.
• Hypothalamus and anterior pituitary are linked by a portal system (links 2 capillary beds; exchange bw blood and tissues occurs in capillaries).

• affect the release of another hormone.
• common tropic hormone pathway
• hypothalamus secretes TH into capillary bed
• blood w TH enters portal vein
• TH accesses anterior pituitary secretory cells via capillary bed.
• AP TH enters bloodstream from same capillary bed, travels to distant endocrine gland, triggers release of hormone.
• control of hypothalamic tropic hormone release is controlled by neural input, by hormones (negative feedback) or by the circadian rhythm.

• Hypothalamic TH, anteriary pituitary TH, target
• PRH(+) or PIH (dopamine)(-), prolactin, breasts
• TRH, TSH, thyroid gland (production of TH) (+)
• CRH(+), ACTH, adrenal cortex (production of cortisol)
• GHRH(+) or GHIH (somatostatin)(-), GH, liver (produce insulin-like growth factors) and other cells throughout the body
• GnRH(+), LH-->Gonads(Male) producing androgens
• GnRH(+), FSH-->Gonads(Female) producing estrogens and progesterones.

• hormone levels must be kept in balance.
• hyposecretion: too little
• hypersecretion: too much

• found in CNS and PNS.
• most abundant NT in PNS.
• Binds to cholinergic receptors on the postsynaptic cell (can be nicotinic or muscarinic)
• Synthesis
• acetyl CoA+choline --> acetylcholine + CoA
• synthesized in cytosol of axon terminal.
• enzyme=CAT=choline acetyl transferase
• Degradation
• acetylcholine --> acetate+choline
• degradation occurs in synaptic cleft
• enzyme=AChE=acetylcholinesterase

• derived from amino acids.
• catecholamines (from tyrosine): dopamine, norepinephrine, epinephrine.
• serotonin (from tryptophan)
• histamine (from histadine).
• Synthesis and Release
• Cytosol of axon terminal, from the AAs listed, packaged in synaptic vesicles.
• Dopamine and norepinephrine common in CNS
• norepinephrine common in PNS
• epinephrine from CNS, more commonly released as hormone.
• serotonin from CNS, brainstem, regulating sleep, emotions.
• histamine from CMS, hypothalamus, most know for paracrine action (allergy)
• Degradation
• Enzymes degrading catecholamines=(1) MAO (monoamine oxidase) and (2) catechol-o-methyltransferase.

• receptors for epinephrine and norepinephrine.
• alpha adrenergic (2 subtypes) and beta drenergic (three subtypes).
• β₂: greatest affinity for epinephrine
• α₁ and β₁: greatest affinity for norepinephrine
• Slow responses at all adrenergic receptors, since they're G protein coupled and usually linked to second messengers.

• at excitatory synapses: aspartate, glutamate
• glutamate receptors: AMPA, kainite, NMDA
• at inhibitory synapses: glycine, GABA
• GABA receptors: A B and C
• most abundant class of NTs in CNS
• GABA is derived from glutamate.

• Neuropeptides=short AA chains, mostly co-located with other neurotransmitters, that modulate the response caused by the other neurotransmitter of co-location.
• ex. endogenous opioids, TRH, vasopressin, oxytocin, substance P
• Other neurotransmitters: purines (ATP), Nitric Oxide