Biol 224 Theme 4

• -mediated by chemical ligands
• -bind to specific recepetors in target cells/tissues
• -slow in general with a prolonged response, (few hours-weeks)

• -signalling molecules synthesized and secreted by specialized cells that are released into the blood and exert specific biochemical actions on the target cells located at distant sites
• -produced by the endocrine glands
• -also produced by the neurons=nuerohormones

• -hormone like molecules released into interstitial space(ecm) exerting biochemical actions on target cells at close sites
• -paracrine regulators

• -regulatory peptides
• -not a "traditional" chemical messenger because they are not produced by a specialized gland
• -can be made by almost any cell that has other primary function
• -can exert local(paracrine) or distant(hormonal) effects

• -produced by neurons that transmit signals across a synapse
• -some can also have hormonal effects
• -are secreted into a virtual compartment called a synapse 
• -information is sent very fast and generally short lived(hormonal effects can last a long time)

• -functional unit of the nervous system
• -generate electrical and chemical signals
• -chemical signals are termed neurotransmitters
• -information is sent very fast and generally short lived

• -when neurotransmitter diffuse through large areas and regulate a diverse population of neurons of the CNS they are neuromodulators 
• -contrasts to classic synaptic transmission(where 1 presynaptic neuron directly influences a single postsynaptic partner)

• -immune cells have specialized markers on the cell membrane that allow transient interaction with cells that have compatible markers
• -phagocytes use this to selectively destroy undesirable cells while leaving healthy cells alone

• -chemical signals released into the environment by an animals glands to affect sensory cells in other animals
• -marking territory
• -mating readiness

-based on a clock found in the superchiasmatic nucleus (SCN) of brain

• -hydrophilic 
• -lipophilic(require protein carriers)
• -gaseous 
• -in blood stream=hormone
• -in synapse=neurotransmitter

• -amines
• -derived from Tryptophan and Tyrosine 
• -some of the neurotransmitters 
• -noradrenalin(norepinephrine, usually a neurotransmitter)
• -adrenaline(epinephrine, usually hormone)
• -serotonin

• -most hormones
• -neurohormones
• -cytokines 
• -growth factors

• -cholesterol derivatives
• -from gonads and adrenal cortex glands
• -less soluble in water(require carriers)

• -derived from vitamin A
• -mainly paracrine regulators
• -involved in development and differentiation

• -derivatives of fatty acids
• -paracrine regulators
• -include prostaglandins which regulate smooth muscle actions among other effects

• -three inorganic gases thought to be toxic are now known to be messengers
• -Nitric oxide, small and highly reactive paracrine signal molecule
• -carbon monoxide, paracrine
• -hydrogen sulfide, paracrine

• -chemical messengers exert effects by binding to receptors
• -messengers can have multiple meanings
• -meaning/response to chemical messenger is determined by the receptor

• -upon ligand binding undergo a conformational change
• -open channels to allow Na or K ion passage creating electrical charge
• -open only briefly and then the ligand dissociates and the receptor is available for binding again

• -also termed G-proteins, coupled receptors
• -cross the cell membrane 7 times
• -associated with a group of regulatory G proteins(called G proteins because they bind to GTP)
• -link the receptor with an intracellular effector enzyme

• -extracellular glycosylated amino-terminal domain(contains binding site)
• -transmembrane domain consisting of seven α helices made up of hydrophobic AA
• -intracellular domain contains AA recognition sequences for the G-proteins also has a C terminal that can be phosphorylated for specific AA which regulate receptor activity

-ligands bind causing the synthesis of an intracellular second messenger that sets off a cascade of phosphorylation reactions that dramatically amplify the extracellular signal

• -associated to effector enzyme adenylyl cyclase (AC) a transmembrane glycoprotein that catalyzes the conversion of ATP into second messenger cAMP
• -three receptors are an example of same key different lock

• -also associated to adenylyl cyclase (AC) (Gαs also associated with AC) but inhibits synthesis of cAMP
• -three receptors are an example of same key different lock

• -associated to effector enzyme phospholipase C-β (PLCβ), a transmembrane protein that's function is to synthesize two second messengers, inositol(1,4,5) triphosphate and diacylglycerol through the membrane phospholipid, phosphatidylinositol
• -three receptors are an example of same key different lock

• -light sensitive compounds
• -odours
• -pheromones 
• -hormones
• -neurotransmitters 
• -for these reasons the seven transmembrane receptors are a target for a large number of modern medicinal drugs

• -receptors located in the cytosol or nucleus are termed nuclear transcription factors hormone receptors 
• -steroid hormone-receptor complex acts as a transcriptional activator to regulate gene activity 
• -can influence a number of genes in a single cell or in different cells through cell-cell communication(gap junctions)

• 1-extracellular first messenger binds to seven transmembrane receptor
• 2-activates Gαs protein(based on first messenger)
• 3-Gαs activates adenylyl cyclase (AC) which converts ATP to cAMP(second messenger)
• 4-cAMP activates protein kinase A (PKA)
• 5-PKA activates(phosphorylates) inactive target protein which brings about cellular response
• -response is through massive amplification, from single first messenger to up to 10 million products of the final activated protein