Enhanced phosphoinositol hydrolysis in response to vasopressin in the septum of the homozygous Brattleboro rat.
Arginine8-vasopressin (AVP) receptors in the septum of the Long-Evans rat have been shown to be both pharmacologically (displacement profiles) and functionally (ability to stimulate phosphoinositide hydrolysis) similar to the peripheral V1-type receptor for AVP. Previous binding studies of AVP receptors in the septum of heterozygous (HE) and homozygous (vasopressin-deficient, HO) Brattleboro (BB) rats revealed an increased number of receptors with a lower affinity for AVP in the HO-BB rat when compared to the HE-BB rat. To determine the effect of these receptor changes in the HO-BB rat septum on the postreceptor response of the tissue to AVP, concentration-response relationships for AVP-stimulated phosphoinositide hydrolysis were examined in septal slices from age-matched, adult male HE- and HO-BB rats. AVP-stimulated accumulation of [3H]inositol-1-phosphate (IP1) was significantly greater in the HO-BB (43.7%) than in the HE-BB (13.7%) at AVP concentrations of 10(-08) to 10(-05) M. The two groups did not, however, differ in their ability to stimulate [3H]IP1 accumulation in response to 2.0 mM carbachol. When the AVP-stimulated phosphoinositide response in both genotypes was compared to that obtained for the Long-Evans (LE) rat (the parent strain of the Brattleboro rat) septum under the same assay condition, it was found that the response in the HE-BB was much lower than in the LE. AVP receptor binding capacity (Bmax) correlated (r = 0.975) with release of IP1 ([3H]IP1 accumulation) for all 3 groups studied (LE, HE, HO).(ABSTRACT TRUNCATED AT 250 WORDS)
Shewey
L M
LM
Department of Pharmacology, University of Washington School of Medicine, Seattle 98195.
Brot
M D
MD
Szot
P
P
Dorsa
D M
DM
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010121:Oxytocin / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011910:Rats, Brattleboro / Q000378:metabolism*; D011922:Rats, Mutant Strains / Q000378:metabolism*; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D017483:Receptors, Vasopressin; D012688:Septum Pellucidum / Q000187:drug effects / Q000378:metabolism*
D010716:Phosphatidylinositols; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D010121:Oxytocin