The Brain Oxytocin Receptor(s?)

Remarkable progress has been made over the past decade in understanding the structure and function of many different peptide receptors.Certainly among these have been the receptors for the neurohypophyseal peptides arginine vasopressin (AVP) and oxytocin (OT).The picture for the AVP receptors seems reasonably clear, with three major subtypes that have been characterized, of which only the V1 subtype has been localized in the brain parenchyma, while the V2 subtype is found in the collecting tubules of the kidney and the V3 subtype predominantly in the anterior pituitary.While the uterine OT receptor has also been well characterized, knowledge of its functions has lagged somewhat behind that of the AVP receptors.This brief commentary will focus on the OT receptor and specifically on brain OT receptors.I will not attempt to recapitulate the excellent reviews which have been published on neurohypophyseal peptides and their receptors over the past 5 years (7,8,24,27,75), but rather I will focus on the interesting and important issues which remain to be resolved about the structure, localization, and function of OT receptor(s) in the brain.As an inducement for all neuroendocrinologists to continue reading, it would be decidedly unusual if many of these questions did not bear relevance to understanding analogous aspects of other peptidergic receptors in the brain as well. STRUCTURE OF OT RECEPTORSTo date only a single OT receptor (OTR) has been cloned from any species.OTR structures have been identified for the human (28), pig (15), rat (52), sheep (50), cow (9), mouse (29), and rhesus monkey (53).All of the cloned receptors are classic G-protein-coupled receptors with seven transmembrane-spanning domains and are highly homologous across species.Because of the high density of