Regulation of Vasopressin Receptors and Phosphoinositide Hydrolysis in the Septum of Heterozygous and Homozygous Brattleboro Rats

Abstract

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 [Η]-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 (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 °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.

Arginine Vasopressin‐lnduced Sensitization in Brain: Facilitated Inositol Phosphate Production Without Changes in Receptor Number

“…daily) administration of relatively low doses of AVP but not in animals that received similar weekly or hourly administration. In keeping with this, Shewey et al (25) did not observe the phenomenon of sensitization of AVP-elicited motor effects in animals implanted intraventricularly with an Accurel mini device containing AVP which slowly and continuously released AVP centrally for 5 dais. Similarly, studies utilizing catecholaminergic agonists have also shown that agonistinduced sensitization may be observed following intermittent, low dose treatment regimes, whereas diminished responsiveness (agonist-induced tolerance) may be observed after frequently repeated (or continuous administration), high dose treatments (reviews in 29-3 1).…”

“…Structure-activity studies provided evidence that implicates thc V1 AVP receptor in AVP sensitization in that pretreatmcnt with a VI receptor antagonist has been shown to block AVP sensitization (6,20). In keeping with this, 'radioligand binding techniques (2 1-23) and phosphatidylinositol (PI) assays (24,25), have revealed central AVP receptors which resemble the V1 type in sitcs of the rat brain, including the septal area, in which AVP sensitization has been demonstrated (20).…”

Corticosteroid Regulation of Gene Expression and Binding Characteristics of Vasopressin Receptors in the Rat Brain

“…secretion (Landgraf et al, 1991). data from previous studies in which AVP levels were chronically altered indicated changes in pituitary and, in certain circumstances cerebral, AVP receptors (Antoni et al, 1985;Koch and Lutz-Bucher, 1985;Shewey and Dorsa, 1986;Shewey et al, 1989). A number of reports have suggested that modifications of the glucocorticoid milieu might result in changes in the binding characteristics of pituitary AVP receptors (Antoni et al, 1985, Koch andLutz-Bucher, 1985) and their associated intracellular second messenger systems (Todd and Lightman, 1987).…”

Vasopressin and angiotensin receptors of the medial septal area in the control of mean arterial pressure induced by vasopressin

“…It appears from these studies that the influence of AVP on its receptor is highly complex. [7][8][9] The nature of receptors mediating central cardiovascular effects of AVP is not clear. In the rat and rabbit, central pressor effect appears to be mediated by V 1 -receptors.…”