Vets 111/Biov 111 Cell Signalling-1. Hormones, Neurotransmitters and Local Mediators

Transcription

1 Vets 111/Biov 111 Cell Signalling-1 Hormones, Neurotransmitters and Local Mediators

2 Why do cells need to communicate and signal? In unicellular organisms every cell is capable of the full range of biochemical processes. In multicellular organisms labour is divided between differentiated cells specialized for particular purposes. As a consequence, close cooperation is required between cells in order for the organism to function efficiently.

3 In mammals, adipose cells store high energy fuel required during periods of starvation or exercise. However, adipose cells have a very low energy requirement and the stored fatty acids are required instead by other cells (e.g. muscle). There must be a means for the rest of the body to signal these requirements to the adipose cells. This is achieved by changes in the concentration of chemical messengers such as adrenaline and insulin.

4 Cells communicate via extracellular signal molecules or first/primary messengers, which are secreted by one cell and can cause a response in another cell which may be some distance away. Hormones are just one example of first (or primary) messengers - other first messengers include the neurotransmitters and the local mediators.

5 Primary messengers can be classified according to the distance over which they act. Endocrine hormones act on cells distant from the site of their secretion. These hormones, like insulin and adrenaline are synthesized and released into the bloodstream by specialized ductless endocrine glands.

6 The endocrine system enables the body to: Maintain homeostasis e.g. insulin and glucagon maintain the blood glucose level within tight limits - irrespective of food intake. Respond to a wide variety of external stimuli - such as the use of adrenaline and noradrenaline in the preparation for fight or flight. Follow various cyclic and developmental programs sex hormones regulate sexual differentiation, maturation, the menstrual cycle and pregnancy.

7 Insulin is secreted from islet cells in the pancreas. In insulin-dependent diabetes (type 1) an autoimmune response selectively destroys islet cells. Typically, the disease develops over several years as the immune system slowly destroys islet cells. Only when > 80% of these cells are destroyed do the classic symptoms of diabetes emerge.

8 Diabetes in pets Diabetes mellitus is a common disorder in cats and dogs (1 in 100 to 1 in 500 pets affected). Type 1 diabetes (destruction of islet cells) is the most common form in pets. Most dogs with diabetes are type 1 and 50-70% of diabetic cats are type 1. Treatment involves daily injection with insulin. In dogs, the cause of type 1 diabetes is usually immune-mediated destruction of the - cells. In cats, amyloidosis the deposition of amylin (also known as islet amyloid polypeptide or IAPP) in the pancreas is the more usual cause. Pets also suffer from type 2 diabetes characterised by insulin resistance in target tissues rather than the destruction of -cells. Treatments include dietary therapy and exercise.

9 Paracrine (from the Greek para - beside) hormones (also known as local mediators) act only on cells close to the cell that released them. Local mediators differ from neurotransmitters in that they are released in a non-directional manner into the extracellular space, rather than into the defined space of the synaptic cleft. Prostaglandins, histamine and many polypeptide growth factors are examples of this class.

10 The use of aspirin as an analgesic (pain-relieving), anti-pyretic (feverreducing) and anti-inflammatory agent is widespread. Aspirin, like other nonsteroidal anti-infammatory drugs (NSAIDs) inhibits the synthesis of prostaglandin from arachidonic acid. Note. Asprin is extremely toxic to cats it cannot be safely metabolized.

11 Autocrine hormones act on the same cell that released them. Interleukin-2, which stimulates T cell proliferation, is an example.

12 Cytotoxic T cell. Macrophage Interleukin-2 production T cells that bind to a macrophage displaying an antigen are induced to propagate. This process is enhanced by the T cells auto-stimulatory secretion of interleukin-2. T cells only express interleukin-2 receptors while bound to a macrophage thereby preventing unlimited T cell proliferation.

13 Neurotransmitters Primary messengers released by nerve cells. Nerve cells can be thought of as being like endocrine cells which have a long extension (axon) by means of which the primary messenger is released very close to the target cell. The nerve impulse travels down the axon to signal the release of neurotransmitter from storage vesicles. Include compounds like noradrenaline also a hormone (released, with adrenaline, from the adrenal gland).

14 Biochemical communications are not limited to intracellular and intercellular signals. Many organisms release pheromones that alter the behaviour of other organisms of the same species in much the same way as hormones. Pheromones are common sexual attractants. The complex social interactions of species such as ants are dependent on pheromones.

15 The plasma membrane.

16 Water-soluble hormones This group of hormones includes the polypeptides (e.g. insulin and glucagon) and the catecholamines (e.g. adrenaline) derived from amino acids. The water-soluble nature of these hormones means that they cannot penetrate the hydrophobic environment of the plasma membrane if a target cell is to respond to one of these hormones it must possess the appropriate cell-surface receptors. Adrenaline (R=CH 3 ) and noradrenaline (R=H).

17 Only those cells with specific receptors for a given hormone will respond to its presence even though nearby cells may also be exposed to the hormone. i.e. hormonal messages are specifically addressed. Receptors typically bind hormones with great specificity and high affinity. The circulating concentrations of hormones are usually extremely low ( M). The -adrenergic receptor

18 Lipid-soluble hormones This group of hormones includes the steroid hormones (based on the structure of cholesterol) because of their lipidsolubility they easily cross the plasma membrane and enter the cytosol of cells. Nonetheless, these hormones still require specific receptors to signal their presence in this case the receptors are present within the cytosol (and nucleus) of target cells.

19 Summary In multicellular organisms, cells communicate with each other using signal or messenger molecules. Endocrine hormones are just one example of primary messenger molecule. Most hormones are either polypeptides, amino acid derivatives (e.g. catecholamines) or steroids. Only those cells with specific receptors for a given hormone will respond to its presence.