Interaction of a vasopressin antagonist with vasopressin receptors in the septum of the rat brain.
The ability of d(CH2)5-Tyr(Me)-arginine-8-vasopressin, an antagonist of peripheral pressoric (V1-type) vasopressin receptors, to label vasopressin binding sites in the septum of the rat brain was evaluated. Using crude membrane preparations from the septum, 3H-arginine-8-vasopressin (AVP) specifically labels a single class of binding sites with a Kd of 2.9 nM and maximum binding site concentration of 19.8 fmole/mg protein. 3H-Antag also labels a single class of membrane sites but with higher affinity (Kd = 0.47 nM) and lower capacity (10.1 fmole/mg protein) than 3H-AVP. The rank order of potency of various competitor peptides for 3H-AVP and 3H-Antag binding was similar. Oxytocin was 100-1,000 fold less potent than AVP in competing for binding with both ligands. 3H-AVP and 3H-Antag showed similar labeling patterns when incubated with septal tissue slices. Unlabeled Antag also effectively antagonized vasopressin-stimulated phosphatidylinositol hydrolysis in septal tissue slices.
Dorsa
D M
DM
Geriatric Research, Education, and Clinical Center, Veterans Administration Medical Center, Seattle, WA 98108.
Brot
M D
MD
Shewey
L M
LM
Meyers
K M
KM
Szot
P
P
Miller
M A
MA
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D017483:Receptors, Vasopressin; D014316:Tritium
D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014316:Tritium; D001127:Arginine Vasopressin; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-