Two splicing variants of a novel family of octopamine receptors with different signaling properties

Abstract

The octopamine and tyramine, as the invertebrate counterparts of the vertebrate adrenergic transmitters, control and modulate many physiological and behavioral processes. Both molecules mediate their effects by binding to specific receptors belonging to the superfamily of G-protein-coupled receptors. So far, four families of octopamine and tyramine receptors have been reported. Here, we described the functional characterization of one putative octopamine/tyramine receptor gene from the rice stem borer, Chilo suppressalis. By a mechanism of alternative splicing, this receptor gene (CsOA3) encodes two molecularly distinct transcripts, CsOA3S and CsOA3L. CsOA3L differs from CsOA3S on account of the presence of an additional 30 amino acids within the third intracellular loop. When heterologously expressed, both receptors cause increases of intracellular Ca 2+ concentration. The short form, CsOA3S, was activated by both octopamine and tyramine, resulting in decreased intracellular cAMP levels ([cAMP] i ) in a dose-dependent manner, whereas dopamine and serotonin are not effective. However, CsOA3L did not show any impact on [cAMP] i . Studies with series of agonists and antagonists confirmed that CsOA3 has a different pharmacological profile from that of other octopamine receptor families. The CsOA3 is, to our knowledge, a novel family of insect octopamine receptors.

Disruption of aminergic signalling reveals novel compounds with distinct inhibitory effects on mosquito reproduction, locomotor function and survival

“…As expected the aminergic GPCRs of two dipteran GPCRs were closer related to each other than to the human GPCRs and formed clusters that have been classified previously282930. Our bootstrapping analysis further supported clades formed by the insect dopaminergic receptors (Dop1, Dop3), serotonergic receptors (5HT1,5,7) and α2 adrenergic-like octopamine receptors (OA3) with the respective human D1, D2, 5-HT and α2 adrenergic receptors.…”

“…Potentially these effects could be caused either by an increased imbalance between the different aminergic systems or by dopamine binding also to the respective adrenergic or serotonergic receptors thereby aggravating the effect caused by tyramine, clonidine or amitriptyline alone. The latter hypothesis is supported by studies which found that dopamine is an Oct α2R (OA3), TyR1 and TyR3 agonist in the insect nervous system3038. However, it also seems plausible that a balance of these systems is essential as often different biogenic amines have opposing effects on behaviours such as egg laying and locomotion in insects2539.…”

Molecular features and expression profiles of octopamine receptors in the brown planthopper, Nilaparvata lugens

“…It exerts its activity via the activation of G‐protein coupled receptors. In insects, the family of octopamine receptors has been characterized comprehensively in recent years . It is believed that the octopaminergic system is unique to invertebrate physiology, so its receptors have been proposed to provide targets for invertebrate‐specific pesticides with potential for low vertebrate toxicity …”

Identification of multiple functional receptors for tyramine on an insect secretory epithelium

“…Multiple types of insect G-protein coupled receptors are activated by TA; these receptors have been classified into three groups of OA receptors and three groups of TA receptors according to a system proposed by Evans and Maqueira 28 and subsequently modified 29–31 . TA can act as an agonist of many OA receptor subtypes, but the OA receptors show varying degrees of selectivity for OA over TA 31–37 .…”

“…TA can act as an agonist of many OA receptor subtypes, but the OA receptors show varying degrees of selectivity for OA over TA 31–37 . The first subtype of TA receptor, the “Oct-TyrR” receptor class, recently renamed TAR1 receptors 29 , is activated with a weak selectivity for TA over OA 38–44 .…”