Presentation Details
| AChemS Undergrad Finalist: Identification of an olfactory receptor involved in newborn rabbits’ responsiveness to the mammary pheromone: molecular genetic evidence Victoria Ko1, Gérard Coureaud2, Patricia Duchamp-Viret2, Hiroaki Matsunami1. 1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, Durham, NC, USA.2Lyon Neuroscience Research Center - ENES team, CNRS/Inserm/Lyon 1 and Jean Monnet Universities, Lyon, France |
Abstract
Successful mammalian development depends on a newborn’s ability to locate the mother’s milk and initiate sucking. In European rabbits (O. cuniculus), this behavior is driven by olfactory cues through the detection of a pheromone present in the mother’s milk. Exposure to mammary pheromone (MP, 2-methylbut-2-enal) elicits typical head searching - oral grasping behavior in rabbit pups (Schaal, Coureaud et al. 2003). Through pS6 IP-Seq together with heterologous cell assays, we identified olfactory receptor 2D2-like as responsive to MP (EC50 10-4.5 M), which we designate as a mammary pheromone receptor (MPR). However, whether MPR mediates newborn behavior remains unclear. We aimed to identify an antagonist for MPR to investigate whether receptor inhibition also inhibits newborn behavior. We used a heterologous cell system to express the olfactory receptor and stimulated with each chemical. Olfactory receptor activities were measured with Glosensor cAMP assays. Through screening a panel of 366 odorants, we identified two compounds, damascenone (Da) and β-ionone (β) (Da IC50 9.75×10-5 M, β IC50 2.72×10-5 M), as both potent and effective antagonists to MPR in the presence of MP. The antagonistic effect was observed to be dose-dependent for both β and Da. To determine the selectivity, MPR was also stimulated with ethyl isobutyrate (EI). EI had no effect on MPR activity alone and did not inhibit the receptor in the presence of MP. In vivo, exposure to Da or β, but not EI, suppressed pups’ sucking-related responses to MP at moderate concentrations (Coureaud et al., this conference). Together, these findings indicate that MPR is a key mediator of MP processing and behavioral responsiveness to MP in newborn rabbits, and provide new insight into the molecular basis of early olfactory-driven behavior.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
Content Locked. Log into a registered attendee account to access this presentation.