Octopamine (OA) and tyramine (TA) are the invertebrate counterparts of the vertebrate adrenergic transmitters They are decarboxylation products of the amino acid tyrosine, with TA as the biological precursor of OA Nevertheless, both compounds are independent neurotransmitters that act through G protein-coupled receptors OA modulates a plethora of behaviors and peripheral and sense organs, enabling the insect to respond correctly to external stimuli Because these two phenolamines are the only biogenic amines whose physiological significance is presumably restricted to invertebrates, pharmacologists have focused their attention on the corresponding receptors, which are still believed to represent promising targets for new insecticides Recent progress made on all levels of OA and TA research has enabled researchers to understand better the molecular events underlying the control of complex behaviors

Tyramine and octopamine: ruling behavior and metabolism.

A review of neurohormone GPCRs present in the fruitfly Drosophila melanogaster and the honey bee Apis mellifera.

Classical biogenic amines (adrenaline, noradrenaline, dopamine, serotonin and histamine) interact with specific families of G protein-coupled receptors (GPCRs). The term 'trace amines' is used when referring to p-tyramine, beta-phenylethylamine, tryptamine and octopamine, compounds that are present in mammalian tissues at very low (nanomolar) concentrations. The pharmacological effects of trace amines are usually attributed to their interference with the aminergic pathways, but in 2001 a new gene was identified, that codes for a GPCR responding to p-tyramine and beta-phenylethylamine but not to classical biogenic amines. Several closely related genes were subsequently identified and designated as the trace amine-associated receptors (TAARs). Pharmacological investigations in vitro show that many TAAR subtypes may not respond to p-tyramine, beta-phenylethylamine, tryptamine or octopamine, suggesting the existence of additional endogenous ligands. A novel endogenous thyroid hormone derivative, 3-iodothyronamine, has been found to interact with TAAR1 and possibly other TAAR subtypes. In vivo, micromolar concentrations of 3-iodothyronamine determine functional effects which are opposite to those produced on a longer time scale by thyroid hormones, including reduction in body temperature and decrease in cardiac contractility. Expression of all TAAR subtypes except TAAR1 has been reported in mouse olfactory epithelium, and several volatile amines were shown to interact with specific TAAR subtypes. In addition, there is evidence that TAAR1 is targeted by amphetamines and other psychotropic agents, while genetic linkage studies show a significant association between the TAAR gene family locus and susceptibility to schizophrenia or bipolar affective disorder.

https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0706948

Trace amine-associated receptors and their ligands.

Trace amines are endogenous compounds classically regarded as comprising β-phenylethyalmine, p-tyramine, tryptamine, p-octopamine, and some of their metabolites. They are also abundant in common foodstuffs and can be produced and degraded by the constitutive microbiota. The ability to use trace amines has arisen at least twice during evolution, with distinct receptor families present in invertebrates and vertebrates. The term "trace amine" was coined to reflect the low tissue levels in mammals; however, invertebrates have relatively high levels where they function like mammalian adrenergic systems, involved in "fight-or-flight" responses. Vertebrates express a family of receptors termed trace amine-associated receptors (TAARs). Humans possess six functional isoforms (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9), whereas some fish species express over 100. With the exception of TAAR1, TAARs are expressed in olfactory epithelium neurons, where they detect diverse ethological signals including predators, spoiled food, migratory cues, and pheromones. Outside the olfactory system, TAAR1 is the most thoroughly studied and has both central and peripheral roles. In the brain, TAAR1 acts as a rheostat of dopaminergic, glutamatergic, and serotonergic neurotransmission and has been identified as a novel therapeutic target for schizophrenia, depression, and addiction. In the periphery, TAAR1 regulates nutrient-induced hormone secretion, suggesting its potential as a novel therapeutic target for diabetes and obesity. TAAR1 may also regulate immune responses by regulating leukocyte differentiation and activation. This article provides a comprehensive review of the current state of knowledge of the evolution, physiologic functions, pharmacology, molecular mechanisms, and therapeutic potential of trace amines and their receptors in vertebrates and invertebrates.

https://pharmrev.aspetjournals.org/content/pharmrev/70/3/549.full.pdf

Trace Amines and Their Receptors.

A genome-wide inventory of neurohormone GPCRs in the red flour beetle Tribolium castaneum.

Biogenic amines and their receptors regulate and modulate many physiological and behavioural processes in animals. In vertebrates, octopamine is only found in trace amounts and its function as a true neurotransmitter is unclear. In protostomes, however, octopamine can act as neurotransmitter, neuromodulator and neurohormone. In the honeybee, octopamine acts as a neuromodulator and is involved in learning and memory formation. The identification of potential octopamine receptors is decisive for an understanding of the cellular pathways involved in mediating the effects of octopamine. Here we report the cloning and functional characterization of the first octopamine receptor from the honeybee, Apis mellifera. The gene was isolated from a brain-specific cDNA library. It encodes a protein most closely related to octopamine receptors from Drosophila melanogaster and Lymnea stagnalis. Signalling properties of the cloned receptor were studied in transiently transfected human embryonic kidney (HEK) 293 cells. Nanomolar to micromolar concentrations of octopamine induced oscillatory increases in the intracellular Ca2+ concentration. In contrast to octopamine, tyramine only elicited Ca2+ responses at micromolar concentrations. The gene is abundantly expressed in many somata of the honeybee brain, suggesting that this octopamine receptor is involved in the processing of sensory inputs, antennal motor outputs and higher-order brain functions.

Lore Grohmann

Papers

Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain.