Chemical transmission
Classification of endocrine
hormones Hormones are chemical messengers. They may be classified several
ways (Fig. 2a):
1. Autocrine:
acting on the cells that synthesized them; for example insulin-like growth
factor (IGF-1) which stimulates cell division in the cell which produced it.
2. Paracrine:
acting on neigh bouring cells. An
example is insulin, secreted by pancreatic b cells and affecting secretion of
glucagon by pancreatic a cells.
3. Endocrine:
acting on cells or organs to which they are carried in the bloodstream or
through another aqueous ducting system, such as lymph. Examples include
insulin, estradiol and cortisol.
4. Neuroendocrine:
this is really paracrine or endocrine, except that the hormones are synthesized
in a nerve cell (neurone) which releases the hormone adjacent to the target
cell (paracrine), or releases it into the bloodstream, which carries it to the
target cell, for example from the hypothalamus to the anterior pituitary gland
through the portal system.
5. Neural:
this is neurotransmission, when a chemical is released by one neurone and acts
on an adjacent neurone (Fig. 2b). These chemicals are termed neurotransmitters.
Neurotransmitters produce virtually instantaneous effects, for example
acetylcholine, whereas some chemicals have a slower onset but longer lasting
effect on the target organ, and are termed neuromodula- tors, for
example certain opioids.
6. Pheromonal
transmission is the release of volatile hormones, called pheromones, into
the atmosphere, where they are transmitted to another individual and are
recognized as an olfactory signal.
Basic principles of neurotransmission When the nerve impulse
arrives at the terminal, it triggers a calcium-dependent fusion of neurotransmitter
packets or vesicles with the nerve terminal plasma membrane (Fig. 2b), followed
by release of the neurotransmitter into the gap, or synapse, between the nerve
cells. The neurotransmitters and neuromodulators bind to specific plasma
membrane receptors, which transmit
the information that the neurotransmitter has brought to the receiving cell by
means of other membrane proteins and intracellular ‘second messengers’. The
neurotransmitters are inactivated by enzymes or taken up into the nerve that
released them and metabolized. The release of the neurotransmitter may be
modulated and limited by: (i) autoreceptors on the nerve terminal from which it
was released, so that further release of the neurotransmitter is inhibited; and
(ii) by presynaptic inhibition, when another neurone synapses with the nerve
terminal.
Chemical Transport
The movement of chemicals between cells and organs is usually tightly
controlled.
Diffusion is the movement of molecules in a fluid phase, in random
thermal (Brownian) motion (Fig. 2c). If two solutions containing the same
chemical, one concentrated and the other relatively dilute, are separated by a
membrane which is completely permeable and passive, the concentrations of the
chemical on either side of the membrane will eventually end up being the same
through simple diffusion of solutes. This is because there are many molecules
of the chemical on the concentrated side, and therefore a statistically greater
probability of movement from the more concentrated side to the more dilute side
of the membrane. Eventually, when the concentrations are equal on both sides,
the net change on either side becomes zero. Lipophilic molecules such as ethyl
alcohol and the steroids, for example estradiol, appear to diffuse freely
across all biological membranes.
Facilitated transport is the transport of chemicals across
membranes by carrier proteins. The process does not require energy and cannot,
therefore, transport chemicals against a concentration gradient. The numbers of
transporter proteins may be under hormonal control. Glucose is carried into the
cell by transporter proteins (see Chapter 39) whose numbers are increased by
insulin.
Active transport uses energy in the form of adenosine tri-
phosphate (ATP) or other metabolic fuels. Therefore chemicals can be
transported across the membrane against a concentration gradient, and the
transport process can be interrupted by metabolic poisons.
Ion channels mediate active transport, and consist of proteins containing
charged amino acids that may form activation and inactivation ‘gates’. Ion channels may be activated by
receptors, or by voltage changes through the cell membrane. Channels of the ion
Ca2+ can be activated by these two methods.
Osmosis is the passive movement of water through a semi- permeable
membrane, from a compartment of low solute con- centration to one which has a
greater concentration of the solute. (‘Solute’ refers to the chemical which is
dissolved in the ‘solvent’, usually water in biological tissues.) Cells will
shrink or swell depending on the concentrations of the solutes on either side
of the membrane.
Phagocytosis and pinocytosis are both examples of endocytosis.
Substances can enter the cell without having to pass through the cell membrane.
Phagocytosis is the ingestion or ‘swallowing’ of a solid particle by a cell,
while pinocytosis is the ingestion of fluid. Receptor-mediated endocytosis is
the ingestion of specifically recognized substances by coated pits. These are
parts of the membrane which are coated with specific membrane proteins, for
example clathrin. Exocytosis is the movement of substances, such as
hormones, out of the cell. Chemicals which are stored in the small vesicles or
packets are secreted or released from the cell in which they are stored by
exocytosis, when the vesicle fuses with the membrane.
Hormone transport in blood. When hormones are secreted into the
blood, many are immediately bound to plasma proteins (Fig. 2d). The proteins
may recognize the hormone specifically and bind it with high affinity and
specificity, for example the binding of sex hormones by sex hormone-binding
globulin (SHBG). Other proteins, such as albumin, also bind many hormones,
including thyroid hormone and the sex hormones, with much lower affinity.
Equilibrium is set up between the free and bound hormone, so that a fixed
proportion of the hormone travels free and unbound, while most is carried
bound. It is currently believed that only the free fraction of the hormone is
physiologically active and available to the tissues and for metabolism. When a
hormone is bound to plasma proteins it is physiologically inactive and is also
protected from metabolic enzymes in organs such as the liver. Some drugs, such
as aspirin, can displace other substances such as anticoagulants from their
binding sites, which in the case of anticoagulants may cause haemorrhage.
