Vets 111/Biov 111 – Cell Signalling-1

Hormones, Neurotransmitters and Local

Mediators

Why do cells need tocommunicate and signal?

In unicellular organisms everycell is capable of the full rangeof biochemical processes.

In multicellular organismslabour is divided betweendifferentiated cells specializedfor particular purposes.

As a consequence, closecooperation is required betweencells in order for the organismto function efficiently.

In mammals, adipose cellsstore high energy fuelrequired during periods ofstarvation or exercise.However, adipose cells have avery low energy requirementand the stored fatty acids arerequired instead by othercells (e.g. muscle).

There must be a means forthe rest of the body to signalthese requirements to theadipose cells. This is achievedby changes in theconcentration of chemicalmessengers such as adrenalineand insulin.

Cells communicate via extracellular signal molecules orfirst/primary messengers, which are secreted by one celland can cause a response in another cell which may besome distance away.

Hormones are just one example of first (or primary)messengers - other first messengers include theneurotransmitters and the local mediators.

Primary messengers canbe classified accordingto the distance overwhich they act.

Endocrine hormonesact on cells distantfrom the site of theirsecretion. Thesehormones, like insulinand adrenaline aresynthesized andreleased into thebloodstream byspecialized ductlessendocrine glands.

The endocrine system enablesthe body to:

Maintain homeostasis e.g.insulin and glucagon maintain theblood glucose level within tightlimits - irrespective of foodintake.

Respond to a wide variety ofexternal stimuli - such as the useof adrenaline and noradrenaline inthe preparation for ‘fight orflight’.

Follow various cyclic anddevelopmental programs – sexhormones regulate sexualdifferentiation, maturation, themenstrual cycle and pregnancy.

Insulin is secreted from isletcells in the pancreas.

In insulin-dependent diabetes(type 1) an autoimmune responseselectively destroys islet cells.

Typically, the disease developsover several years as the immunesystem slowly destroys islet cells.Only when > 80% of these cellsare destroyed do the classicsymptoms of diabetes emerge.

Diabetes in pets

Diabetes mellitus is a common disorder in catsand dogs (1 in 100 to 1 in 500 pets affected).

Type 1 diabetes (destruction of islet cells) isthe most common form in pets. Most dogs withdiabetes are type 1 and 50-70% of diabetic catsare type 1. Treatment involves daily injectionwith insulin.

In dogs, the cause of type 1 diabetes isusually immune-mediated destruction of the -cells. In cats, amyloidosis – the deposition ofamylin (also known as islet amyloid polypeptideor IAPP) in the pancreas is the more usualcause.

Pets also suffer from type 2 diabetes –characterised by insulin resistance in targettissues – rather than the destruction of -cells.Treatments include dietary therapy andexercise.

Paracrine (from the Greek para -beside) hormones (also known aslocal mediators) act only on cellsclose to the cell that releasedthem.

Local mediators differ fromneurotransmitters in that they arereleased in a non-directionalmanner into the extracellularspace, rather than into the definedspace of the synaptic cleft.

Prostaglandins, histamine andmany polypeptide growth factorsare examples of this class.

The use of aspirin as an analgesic (pain-relieving), anti-pyretic (fever-reducing) and anti-inflammatory agent is widespread. Aspirin, likeother nonsteroidal anti-infammatory drugs (NSAIDs) inhibits thesynthesis of prostaglandin from arachidonic acid. Note. Asprin isextremely toxic to cats – it cannot be safely metabolized.

Autocrine hormones act onthe same cell that releasedthem. Interleukin-2, whichstimulates T cellproliferation, is an example.

Macrophage

Cytotoxic T cell.

Interleukin-2 production

T cells that bind to a macrophage displaying an antigen areinduced to propagate. This process is enhanced by the T cells’auto-stimulatory secretion of interleukin-2. T cells only expressinterleukin-2 receptors while bound to a macrophage therebypreventing unlimited T cell proliferation.

Neurotransmitters

Primary messengers released bynerve cells.

Nerve cells can be thought of asbeing like endocrine cells whichhave a long extension (axon) bymeans of which the primarymessenger is released very closeto the target cell.

The nerve impulse travels downthe axon to signal the release ofneurotransmitter from storagevesicles.

Include compounds likenoradrenaline – also a hormone(released, with adrenaline, fromthe adrenal gland).

Biochemical communicationsare not limited to intracellularand intercellular signals. Manyorganisms release pheromonesthat alter the behaviour ofother organisms of the samespecies in much the same wayas hormones.

Pheromones are commonsexual attractants.

The complex socialinteractions of species such asants are dependent onpheromones.

The plasma membrane.

Water-soluble hormones

This group of hormonesincludes the polypeptides (e.g.insulin and glucagon) and thecatecholamines (e.g. adrenaline)– derived from amino acids.

The water-soluble nature ofthese hormones means thatthey cannot penetrate thehydrophobic environment of theplasma membrane – if a targetcell is to respond to one ofthese hormones it must possessthe appropriate cell-surfacereceptors.

Adrenaline (R=CH3) and noradrenaline (R=H).

Only those cells withspecific receptors for agiven hormone will respondto its presence even thoughnearby cells may also beexposed to the hormone. i.e.hormonal messages arespecifically addressed.

Receptors typically bindhormones with greatspecificity and highaffinity.

The circulatingconcentrations of hormonesare usually extremely low(10-9 -10-12M). The -adrenergic receptor

Lipid-soluble hormones

This group of hormonesincludes the steroidhormones (based on thestructure of cholesterol) –because of their lipid-solubility they easily crossthe plasma membrane andenter the cytosol of cells.

Nonetheless, thesehormones still requirespecific receptors to signaltheir presence – in this casethe receptors are presentwithin the cytosol (andnucleus) of target cells.

Summary

In multicellular organisms, cells communicate with each otherusing signal or messenger molecules.

Endocrine hormones are just one example of primary messengermolecule.

Most hormones are either polypeptides, amino acid derivatives(e.g. catecholamines) or steroids.

Only those cells with specific receptors for a given hormone willrespond to its presence.