More than 20 years ago, an oxytocin/vasopressin-like peptide, CLITNCPRGamide, was isolated from the locust,
Locusta migratoria
[Proux JP,
et al.
(1987) Identification of an arginine vasopressin-like diuretic hormone from
Locusta migratoria. Biochem Biophys Res Commun
149:180–186]. However, no similar peptide could be identified in other insects, nor could its prohormone be cloned, or its physiological actions be established. Here, we report that the recently sequenced genome from the red flour beetle
Tribolium castaneum
contains a gene coding for an oxytocin/vasopressin-like peptide, identical to the locust peptide, which we named inotocin (for insect oxytocin/vasopressin-like peptide) and a gene coding for an inotocin G protein-coupled receptor (GPCR). We cloned the
Tribolium
inotocin preprohormone and the inotocin GPCR and expressed the GPCR in CHO cells. This GPCR is strongly activated by low concentrations of inotocin (EC
50
, 5 × 10
−9
M), demonstrating that it is the inotocin receptor. Quantitative RT-PCR (qPCR) showed that in adult
Tribolium
, the receptor is mainly expressed in the head and much less in the hindgut and Malpighian tubules, suggesting that the inotocin/receptor couple does not play a role in water homeostasis. Surprisingly, qPCR also showed that the receptor is 30× more expressed in the first larval stages than in adult animals. The inotocin/receptor couple can also be found in the recently sequenced genome from the parasitic wasp
Nasonia vitripennis
but not in any other holometabolous insect with a completely sequenced genome (
12Drosophila
species, the malaria mosquito
Anopheles gambiae
, the yellow fever mosquito
Aedes aegypti
, the silk worm
Bombyx mori
, and the honey bee
Apis mellifera
), suggesting that this neuropeptide system is confined to basal holometabolous insects. Furthermore, we identified an oxytocin/vasopressin-like peptide and receptor in the recently sequenced genome from the water flea
Daphnia pulex
(Crustacea). To our knowledge, this is the first report on the molecular cloning of an oxytocin/vasopressin-like receptor and its ligand from arthropods.
