Guanine nucleotide regulation and cation sensitivity of agonist binding to rat brain oxytocin receptors

Abstract

The neuropeptide oxytocin (OT) is synthesized in the hypothalamus and can be released either as a hormone from the neurohypophysis or as a neurotransmitter in various brain regions. The present studies were undertaken to better characterize the pharmacological properties of brain oxytocin receptors (OTRs) using a radioligand selective for OTRs. Based on kinetic analysis, brain membranes obtained from 10-day-old rats display rapid and reversible binding to this ligand. In addition, saturation isotherm studies demonstrated that binding was saturable and of high affinity. Indicative of the selectivity of these receptors, compounds known to he ligands for OTRs in other tissues were able to displace the radioligand with high affinity. Consistent with the divalent cation requirement of OTRs in other tissues, OT binding was greatly reduced in rat brain membranes by the removal of magnesium from the incubation. To examine the possible GTP regulation of these receptors, binding was examined in the presence of a GTP analog. High affinity agonist, but not antagonist, binding was reduced by the GTP analog, indicating that these OTRs are likely to be associated with G proteins.