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NEUROHUMORAL TRANSMISSION


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It implies that nerves transmit their message across synapses and neurones effector junctions by the release of humoral or chemical messengers known as neurotransmitters.

A neurotransmitter is a chemical mediator which transmits nerve impulses across junctions. To be consider d as a post junctionally acting neurotransmitter, a substance must fulfill the following criteria:

  1. It should be present in the presynaptic neuron; usually along with the enzyme synthesising it.
  2. The neurotransmitter should be released in the medium following nerve stimulation.
  3. The application of that chemical should produce responses identical to those produced by nerve stimulation.
  4. Its effects should be antagonized or potentiated by other substances which similarly alter effects of nerve stimulation.
  5. There must be a mechanism for rapid determination of the action of the compound; and this mechanism must be identical as the mechanism of inactivation of the endogenously occuring neurotransmitters (substance).

The release of neurotransmitters depends on processes which are triggered by calcium uptake and regulated by phosphorylation or synaptic proteins. The released neurotransmitter rapidly diffuses across the synapse and combines with specific receptors on the post synaptic cell which is usually the target cell. Neurotransmitters can be excitatory or inhibitory depending on the nature of the action it elicits. Following calcium entry, there is a fusion of the vesicular and axonal membranes which results in the extrusion of the vesicular contents (exocytosis). An excitatory neurotransmitter will induce EPSP (excitatory postsynaptic potential; repolarizing potential); an inhibitory neurotransmitter will induce an IPSP (inhibitory postsynaptic potential; hyperpolarizing potential). A suprathreshold EPSP generates a propagated post-synaptic action potential which results in generation of  a nerve impulse in a neuron, contraction in a muscle or secretion in a gland. An IPSP will stabilise a post-synaptic membrane and resist repolarizing stimuli.

There are over 50 neurotransmitters in the CNS, but 6 of them are most actively involved in the actions of drugs used clinically (noradrenaline, acetylcholine, dopamine, serotonin - 5HT, histamine and GABA). Each of these neurotransmitters binds to a specific family of receptors (NB: all neurotransmitters, most hormones and local mediators are too hydrophilic to penetrate the lipid bilayer of the target cell membranes; hence, their receptors are usually on the cell membrane. When they combine with these receptors, their effects are propagated through the cell via second messengers e.g. cAMP, cGMP).

Drugs can affect neurohumoral transmission at various steps by modifying the following processes:

  1. Synthesis, storage or release of neurotransmitters.
  2. Interactions between the neurotransmitter and the receptor.
  3. Enzymatic destruction or reuptake of a neurotransmitter into the neuron.
  4. Transport of a neurotransmitter in the cells.
  5. Recovery of a cell membrane after the transmitter-receptor interaction.

*NB:* VIP- Parasympathetic, Neuropeptide Y- sympathetic.

_*Neuro mediator*_: A neurotransmitter mediator participates in the elicitation or the post-synaptic response to the neurotransmitter.

_*Neuro hormone*_: is a substance that is secreted into the blood by a neuron. E.g. adrenaline is released from the adrenal medulla into the bloodstream under the influence of the pituitary.

*NB:* most receptors and proteinous in nature, but all receptors are not proteins.

*Assignment*

  1. list all the neurohormones in the body and explain why they are neurohormones.
  2. Which receptors are not proteins?