V1-type vasopressin receptors in rat brain septum: binding characteristics and effects on inositol phospholipid metabolism.
Specific binding sites for 3H-arginine8-vasopressin (AVP) have been characterized in rat septal membranes. Scatchard analyses revealed a single class of high-affinity binding sites having an equilibrium dissociation constant of 1.7 +/- 0.3 nM and total binding capacity of 22.6 +/- 4.2 fmol/mg protein. Binding displacement studies with peptide analogs of AVP indicate that this binding site is similar to the V1 (pressor)-type receptor for AVP. When added to rat brain septal slices that had been prelabeled with 3H-myo-inositol, vasopressin stimulated the accumulation of 3H-inositol-1-phosphate (IP1) in the presence of 7 mM lithium. This effect was dose dependent with maximal stimulation (65% over basal) occurring at a concentration of 0.5 microM AVP. Higher concentrations, however, tended to inhibit phosphoinositide hydrolysis. The vasopressin-stimulated accumulation of 3H-IP1 was completely inhibited by the vasopressin V1 antagonist, d(CH2)5[Tyr(Me)2]AVP, in a concentration-dependent manner. Oxytocin, at concentrations of 10(-8) and 10(-5) M, only slightly increased 3H-IP1 accumulation (17-20% over basal). In contrast, the V2 agonist deamino-D-arginine vasopressin (dDAVP), failed to produce significant stimulation of 3H-IP1 accumulation, even at high concentrations. The effects of these analogs on phosphoinositide hydrolysis is consistent with their potencies in displacing 3H-AVP from septal binding sites. These results indicate that vasopressin stimulates hydrolysis of inositol phospholipids in rat brain septum through an interaction with V1-type vasopressin receptors.
Shewey
L M
LM
Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Seattle, Washington 98108.
Dorsa
D M
DM
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism* / Q000494:pharmacology; D001667:Binding, Competitive; D003894:Deamino Arginine Vasopressin / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009994:Osmolar Concentration; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012688:Septum Pellucidum / Q000378:metabolism*
D010716:Phosphatidylinositols; D011956:Receptors, Cell Surface; D001127:Arginine Vasopressin; D010121:Oxytocin; D003894:Deamino Arginine Vasopressin