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 nM carbochol. 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 conditions, it was found that the response in the HE-BB was much lower in the LE, AVP receptor binding capacity (B_max correlated (r = 0.975) with release of IP₁ [³H]P₁ accumulation) for all 3 groups studied (LE, HE, HO). These results indicate that Brattleboro rats do posses functional receptors for AVP in the septum, and that the postreceptor response in the septum of the HO-BB rat is much larger than in the HE-BB rat.