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

Linda M. Shewey, Gerard J. Boer, Patricia Szot, Daniel Dorsa

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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 (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 (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.

Original languageEnglish (US)
Pages (from-to)292-298
Number of pages7
JournalNeuroendocrinology
Volume50
Issue number3
DOIs
StatePublished - 1989
Externally publishedYes

Fingerprint

Brattleboro Rats
Vasopressin Receptors
Arginine Vasopressin
Phosphatidylinositols
Hydrolysis
Down-Regulation
Binding Sites
Cerebral Ventricles
Polypropylenes
Lateral Ventricles
Proteins
Hormones

Keywords

  • Accurel technique
  • AVP receptors
  • Brattleboro rats
  • Phosphoinositide hydrolysis
  • Septum
  • Vasopressin supplementation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Cellular and Molecular Neuroscience
  • Endocrine and Autonomic Systems
  • Neuroscience(all)

Cite this

Regulation of vasopressin receptors and phosphoinositide hydrolysis in the septum of heterozygous and homozygous brattleboro rats. / Shewey, Linda M.; Boer, Gerard J.; Szot, Patricia; Dorsa, Daniel.

In: Neuroendocrinology, Vol. 50, No. 3, 1989, p. 292-298.

Research output: Contribution to journalArticle

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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 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 (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 (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.",
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