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 I 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 (K_D) 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 (IPi) 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 °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]-IPi accumulation (phosphoinositide hydrolysis) of AVP receptors in the septum of the BB rat.