GUANINE-NUCLEOTIDE REGULATION AND CATION SENSITIVITY OF AGONIST BINDING TO RAT-BRAIN OXYTOCIN RECEPTORS

The neuropeptide oxytocin (OT) is synthesized in the hypothalamus and can be released either as a hormone from the neurohypophysis or as a n eurotransmitter in various brain regions. The present studies were und ertaken to better characterize the pharmacological properties of brain oxytocin receptors (OTRs) using a radioligand selective for OTRs. Bas ed on kinetic analysis, brain membranes obtained from 10-day-old rats display rapid and reversible binding to this ligand. In addition, satu ration isotherm studies demonstrated that binding was saturable and of high affinity. Indicative of the selectivity of these receptors, comp ounds known to be ligands for OTRs in other tissues were able to displ ace the radioligand with high affinity. Consistent with the divalent c ation requirement of OTRs in other tissues, OT binding was greatly red uced in rat brain membranes by the removal of magnesium from the incub ation. To examine the possible GTP regulation of these receptors, bind ing was examined in the presence of a GTP analog. High affinity agonis t, but not antagonist, binding was reduced by the GTP analog, indicati ng that these OTRs are likely to be associated with G proteins.