|Synonyms||OCT, Norsympathol, Norsynephrine, para-Octopamine, beta-Hydroxytyramine, para-hydroxy-phenyl-ethanolamine, α-(Aminomethyl)-4 hydroxybenzenemethanol, 1-(p-Hydroxyphenyl)-2-aminoethanol|
|Source tissues||invertebrate nervous systems; trace amine in vertebrates|
|Target tissues||system-wide in invertebrates|
OctαR, OctβR, TyrR (invertebrates), Oct-TyrR
|Agonists||Formamidines (amitraz (AMZ) and chlordimeform (CDM))|
|Antagonists||epinastine (3-amino-9, 13b-dihydro-1H-dibenz(c,f)imidazo(1,5a)azepine hydrochloride)|
|Biosynthesis||tyramine β-hydroxylase; dopamine β-hydroxylase|
|Metabolism||N-acetyltransferases; phenylethanolamine N-methyltransferase|
Octopamine is an organic chemical closely related to norepinephrine, and synthesized biologically by a homologous pathway. Its name derives from the fact that it was first identified in the salivary glands of the octopus.
In many types of invertebrates octopamine is an important neurotransmitter and hormone. In protostomes—arthropods, molluscs, and several types of worms—it substitutes for norephinephrine and performs functions apparently similar to those of norepinephrine in mammals, functions that have been described as mobilizing the body and nervous system for action.
Octopamine exerts its effects by binding to and activating receptors located on the surface of cells. These receptors have mainly been studied in insects, where they can be divided into three types: alpha-adrenergic-like (OctαR), which are structurally and functionally similar to noradrenergic alpha-1 receptors in mammals; beta-adrenergic-like (OctβR), which are structurally and functionally similar to noradrenergic beta receptors in mammals; and mixed octopamine/tyramine receptors (TyrR), which are structurally and functionally similar to noradrenergic alpha-2 receptors in mammals. Receptors in the TyrR class, however, are generally more strongly activated by tyramine than by octopamine.
In vertebrates no octopamine-specific receptors have been identified. Octopamine binds weakly to receptors for norepinephrine and epinephrine, but it is not clear whether this has any functional significance. It binds more strongly to trace amine-associated receptors (TAARs), especially TAAR1.
Octopamine was first discovered by Italian scientist Vittorio Erspamer in 1948 in the salivary glands of the octopus and has since been found to act as a neurotransmitter, neurohormone and neuromodulator in invertebrates. Although Erspamer discovered its natural occurrence and named it, octopamine had actually existed for many years as a pharmaceutical product. It is widely used in energy-demanding behaviors by all insects, crustaceans (crabs, lobsters, crayfish), and spiders. Such behaviors include flying, egg-laying, and jumping.
Octopamine acts as the insect equivalent of norepinephrine and has been implicated in regulating aggression in invertebrates, with different effects on different species. Studies have shown that reducing the neurotransmitter octopamine and preventing coding of tyramine beta hydroxylase (an enzyme that converts tyramine to octopamine) decreases aggression in Drosophila without influencing other behaviors.
The best-understood role for octopamine is in the locust jump. Here it modulates muscle activity, making the leg muscles contract more effectively. This is at least in part due to an increase in the rate of contraction and of relaxation. Octopamine, also has a role in locust flight. A study done in 2014 showed that when a locust was injected with octopamine the acoustic startle response of a locust during flight was changed, and the flight path of the locust was erratic.
In lobsters, octopamine seems to direct and coordinate neurohormones to some extent in the central nervous system, and it was observed that injecting octopamine into a lobster and crayfish resulted in limb and abdomen extension.
The emerald cockroach wasp stings the host for its larvae (a cockroach) in the head ganglion (brain). The venom blocks octopamine receptors and the cockroach fails to show normal escape responses, grooming itself excessively. It becomes docile and the wasp leads it to the wasp's den by pulling its antenna like a leash.
In vertebrates, octopamine replaces norepinephrine in sympathetic neurons with chronic use of monoamine oxidase inhibitors. It may be responsible for the common side effect of orthostatic hypotension with these agents, though there is also evidence that it is actually mediated by increased levels of N-acetylserotonin.
One study noted that octopamine might be an important amine that influences the therapeutic effects of inhibitors such as monoamine oxidase inhibitors, especially because a large increase in octopamine levels was observed when animals were treated with this inhibitor. Octopamine was positively identified in the urine samples of mammals such as humans, rats, and rabbits treated with monoamine oxidase inhibitors. Very small amounts of octopamine were also found in certain animal tissues. It was observed that within a rabbit's body, the heart and kidney held the highest concentrations of octopamine. Octopamine was found to be 93% eluted by urine within 24 hours of being produced in the body as a byproduct of Iproniazid in rabbits.
Octopamine binds to its respective G-protein coupled receptors (GPCRs) to initiate a cell signal transduction pathway. At least three groups of octopamine GPCR have been defined. OctαR (OCTOPAMINE1 receptors) are more closely related to α-adrenergic receptors, while OctβR (OCTOPAMINE2 receptors) are more closely related to β-adrenergic receptors. The Octopamine/Tyramine receptors (including Oct-TyrR) can bind both ligands, and display agonist-specific coupling. Oct-TyrR is listed in both OCTOPAMINE and TYRAMINE RECEPTORS gene groups.
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CNS (region specific) & several peripheral tissues:
Stomach > amygdala, kidney, lung, small intestine > cerebellum, dorsal root ganglion, hippocampus, hypothalamus, liver, medulla oblongata, pancreas, pituitary gland, pontine reticular formation, prostate, skeletal muscle, spleen. ...
Leukocytes ...Pancreatic islet β cells ... Primary Tonsillar B Cells ... Circulating leukocytes of healthy subjects (upregulation occurs upon addition of phytohaemagglutinin).
Species: Human ...
In the brain (mouse, rhesus monkey) the TA1 receptor localises to neurones within the momaminergic pathways and there is emerging evidence for a modulatory role for TA1 on function of these systems. Co-expression of TA1 with the dopamine transporter (either within the same neurone or in adjacent neurones) implies direct/indirect modulation of CNS dopaminergic function. In cells expressing both human TA1 and a monoamine transporter (DAT, SERT or NET) signalling via TA1 is enhanced [26,48,50–51]. ...
Functional Assays ...
Mobilization of internal calcium in RD-HGA16 cells transfected with unmodified human TA1
Response measured: Increase in cytopasmic calcium ...
Measurement of cAMP levels in human cultured astrocytes.
Response measured: cAMP accumulation ...
Activation of leukocytes
Tissue: PMN, T and B cells
Response measured: Chemotactic migration towards TA1 ligands (β-Phenylethylamine, tyramine and 3-iodothyronamine), trace amine induced IL-4 secretion (T-cells) and trace amine induced regulation of T cell marker RNA expression, trace amine induced IgE secretion in B cells.
- "Gene Group : OCTOPAMINE RECEPTORS", FlyBase, October 16, 2018.