Regulation of vasopressin receptors and phosphoinositide hydrolysis in the septum of heterozygous and homozygous Brattleboro rats.

Accurel polypropylene mini-devices, loaded with arginine vasopressin (AVP) and implanted in the lateral cerebral ventricle were used to centrally treat heterozygous (HE) and homozygous (HO) Brattleboro (BB) rats. After 1 week of treatment, the concentration of AVP receptors in the HO-BB rat septum decreased from 19.4 +/- 2.6 to 12.4 +/- 1.1 fmol/mg protein, but remained unchanged in the HE-BB rat (10.7 +/- 0.8 and 7.0 +/- 1.1 fmol/mg protein). In the HO-BB rat the [3H]-AVP equilibrium dissociation constant (KD) of the septal AVP receptor decreased following AVP treatment (from 4.17 +/- 0.7 to 1.97 +/- 0.3 nM) compared to that of control animals. This decrease in receptor number following AVP treatment was accompanied by a decrease in the postreceptor response to AVP as measured by the AVP-stimulation of [3H]-inositol-1-phosphate (IP1) accumulation (22.0 +/- 6.1%) when compared to untreated animals (54.3 +/- 8.3%). This apparent AVP-induced down-regulation was not due to occupancy of the binding sites by AVP since preincubation of the tissue at 37 degrees C for 60 min (which was able to cause near-complete dissociation of the hormone-receptor complex) did not result in an increased number of binding sites upon reexposure to [3H]-AVP. This study thus provides evidence for the homologous down-regulation and desensitization in terms of [3H]-IP1 accumulation (phosphoinositide hydrolysis) of AVP receptors in the septum of the BB rat.