Localization of vasopressin binding sites in rat brain by in vitro autoradiography using a radioiodinated V1 receptor antagonist.
Vasopressin may act in the brain as a neurotransmitter or neuromodulator to influence blood pressure, memory, body temperature and brain development. In order to localize probable central nervous system sites for these actions, we have used 125I-labelled 1-d(CH2)5, 7-sarcosine-8-arginine vasopressin, a specific V1-receptor antagonist, and in vitro autoradiography to map brain vasopressin binding sites. High levels of binding were found in the choroid plexus, blood vessels, lateral septum, bed nucleus of stria terminalis, accumbens nucleus, central nucleus of amygdala, stigmoid hypothalamic nucleus, suprachiasmatic nucleus, arcuate nucleus, nucleus of the solitary tract, area postrema and parts of the hippocampus, thalamus, superior colliculus, and inferior olivary nuclei. Many of these regions are known to be vasopressin-sensitive and to contain vasopressin fibres. Significantly there was no binding to the paraventricular nor the supraoptic nuclei. Displacement of the radioligand from the lateral septum with unlabelled vasopressin analogues gave a rank order of potencies: d(CH2)5-D-Tyr2(Et)Val4-desGly9-arginine-vasopressin approximately equal to d(CH2)5-Tyr2-(Me)arginine-vasopressin approximately equal to arginine-vasopressin approximately equal to d(CH2)5-Sar7-arginine-vasopressin greater than [1-deamino, 8-D-arginine]-vasopressin approximately equal to oxytocin much greater than vasopressin4-9, consistent with binding to V1 receptor subtype. These studies confirm and extend previous findings of V1 receptors in the rat brain. In particular, several new regions of vasopressin receptor binding have been identified, possibly due to the advantages of a radioiodinated ligand with high receptor affinity without binding to neurophysins. Future study of these regions may prove fruitful in elucidating the central actions of vasopressin.
Phillips
P A
PA
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Abrahams
J M
JM
Kelly
J
J
Paxinos
G
G
Grzonka
Z
Z
Mendelsohn
F A
FA
Johnston
C I
CI
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000378:metabolism; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; C058531:argipressin, (1-beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-Sar(7)-; D001127:Arginine Vasopressin