Classification of Neurosecretions

neurotransmitters are released into the synaptic cleft

in order to influence neighboring cells. They have a short range and a short lifespan.
neurohormones are released into the blood, allowing

them to cover larger distances.

The sequence of events that lead to postsynaptic changes is as follows:

The action potential signal arrives at the axon terminal

The local depolarization causes Ca2+ channels to open. Ca2+ enters the presynaptic cell because its concentration is greater outside the cell than inside.The Ca2+, by binding with calmodulin, causes vesicles filled with neurotransmitter to migrate towards the presynaptic membrane.

 The vesicle merges with the presynaptic

membrane.The presynaptic membrane and vesicle now forms a continuous membrane, so that the neurotransmitter is released into the synaptic cleft. This process is called exocytosis. The neurotransmitter diffuses through the synaptic cleft and binds with receptor channel membranes that are located in both presynaptic and postsynaptic membranes. The time period from neurotransmitter release to receptor channel binding is less than a millionth of a second.

Direct and Indirect Binding to Postsynaptic Receptor

There are two kinds of receptor channels: direct and

indirect Direct: the receptor channel allows ions to pass through the membrane. The neurotransmitter acts like a key which opens the ion channel. This is the fastest kind of channel .This is called an ionotropic receptor. If the inflowing ions are cations (Na+, K+, Ca2+), depolarization of the membrane occurs and an action potential is triggered on the surface of the postsynaptic cell. This is the way in which stimulatory transmitters work (e. g., acetylcholine and glutamate).

 By contrast, if anions flow in (mainly Cl), the result is

hyperpolarization of the postsynaptic membrane, which makes the production of a postsynaptic action potential more difficult. The action of inhibitory transmitters such as glycine and -aminobutyric acid (GABA) is based on this effect.

 Indirect: the binding of neurotransmitter to the

receptor channel causes the release of a molecule, called a secondary messenger, that indirectly activates nearby ion channels. This is called a metabotropic receptor.
This process is much slower than direct receptor ion

channels: from 30 ms up to 1 second. However, this is the most common type of postsynaptic receptor channel

Acetylcholine

Acetylcholine

Acetylcholine (ACh) is a simple molecule synthesized from choline and acetyl-CoA through the action of choline acetyltransferase.
Neurons that synthesize and release ACh are termed cholinergic neurons. It acts at neuromuscular junctions, where it triggers muscle contraction, and in certain parts of the brain and in the autonomic nervous system.

Biogenic Amines
Biogenic amines arise from amino acids by

decarboxylation.

Biogenic Amines

Synthesis of Catecholamines

 The neurological disorder Parkinsons disease is

associated with an underproduction of dopamine, and it has traditionally been treated by administering Ldopa.
Overproduction of dopamine in the brain may be

linked to psychological disorders such as schizophrenia

 Catechol O-methyl transferase (COMT) catalyzes the

addition of methyl group, on the benzene ring using Sadenosyl methionine as methyl donor. Monoaminoxidase (MAO) deaminate monoamine. It occurs mainly in liver, stomach, kidney and intestine. One of the principal metabolite of epinephrine and norepinephrine is vanillyl mandelic acid (VMA) which increases in urine of patients with pheochromocytoma (tumour of the adrenal medulla).

Degradation of Catecholamines

Serotonin

Biological functions of serotonin:1- It acts as excitatory chemical transmitter in the brain where it stimulates brain activity and affects behavior. It stimulates release of prolactin. 2- It is present in the mast cells and platelets. It mediates platelet aggregation. 3- It causes smooth muscle contractions in the arterioles (vasoconstriction) and bronchioles. 4- It acts as a transmitter in GIT to release peptide hormones.

Catabolism of serotonin: Oxidative deamination of serotonin by monoamine

oxidase will form 5- hydroxyindole acetic acid (5 HIAA) (normal value 2-8 mg/ 24 hour urine).
The level of serotonin in the brain controls the mood.

An increase in serotonin will cause euphoria while its decreased level will cause depression. In depression, we can give a drug that inhibits monoamine oxidase enzyme to prevent the decrease in serotonin level.

Melatonin
is a hormone, derived from tryptophan, serotonin is an

intermediate. Melatonin is formed in the pineal body tissue and in peripheral nerves and secreted into the blood and CSF.
Melatonin is synthesized in human during the dark

period of the day and maintained at a low level during the day light.

 This diurnal variation is brought about by

norepinephrine that stimulates pineal cells to synthesize melatonin. Norepinephrine increases cAMP which increases N-acetyl transferase activity.

GABA
The amino acid derivative, -aminobutyrate (GABA) is

a well-known inhibitor of presynaptic transmission in the CNS, and also in the retina.
The formation of GABA occurs by the decarboxylation

of glutamate catalyzed by glutamate decarboxylase (GAD). GAD is present in many nerve endings of the brain as well as in the -cells of the pancreas. The activity of GAD requires pyridoxal phosphate (PLP) as a cofactor.

 GABA is degraded by GABA aminotransferase to

succinate semialdehyde that is converted to succinate.

The underproduction of GABA occurs due to GAD or

vitamin B6 deficiency, it is associated with epileptic seizures

Histamine

It is synthesized by decarboxylation of histidine.

- Alanine

It is synthesized by decarboxylation of aspartic acid. - It is a component of carnosine and pantothenic acid.

Peptides
Peptides make up the largest group among the

neurosecretions. Many peptide hormones e. g. angiotensin IIsimultaneously act as transmitters. Most neuropeptides are small (315 AA). Endorphins, and enkephalins are a particularly interesting group of neuropeptides. They act as endogenous opiates by producing analgesic, sedative, and euphoriant effects in extreme situations. Drugs such as morphine and heroin activate the receptors for these peptides.

Purine derivatives
Purine derivatives with neurotransmitter function are

all derived from adenine-containing nucleotides or nucleosides. ATP is released along with acetylcholine and other transmitters, and among other functions it regulates the emission of transmitters from its synapse of origin. The stimulatory effect of caffeine is mainly based on the fact that it binds to adenosine receptors.