(/sup 3/H)AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

Journal Article · Sun May 01 00:00:00 EDT 1988 · Peptides (Fayetteville, N.Y.); (United States)

DOI:https://doi.org/10.1016/0196-9781(88)90170-2· OSTI ID:6681844

Mah, S C; Whitebread, S E; De Gasparo, M; Hofbauer, K G

The interaction of an antagonist of arginine vasopressin (AVP), d(CH2)5-D-Tyr(Et)VAVP, with renal tubular V2 receptors were studied in medullary membrane preparations from kidneys of Sprague-Dawley and Brattleboro rats. In both rat strains, V2 receptors had comparable KD and Bmax values for binding of (3H)AVP. In vitro studies revealed that the V2-antagonist was more potent than cold AVP in displacing (3H)AVP. In vivo treatment of Sprague-Dawley rats with the antagonist over one week resulted only in a transient state of diabetes insipidus (DI). No specific (3H)AVP binding was detectable throughout the period of administration. Chronic treatment of Brattleboro rats resulted in a complete normalization of water intake. This agonistic effect was also associated with undetectable (3H)AVP binding. After stopping the infusion of d(CH2)5-D-Tyr(Et)VAVP, Bmax values tended to rise but had still not reached base line values after 6 days. In contrast, the chronic infusion of AVP in Brattleboro rats resulted in a reduction in water intake which was accompanied by a decreased Bmax. (3H)AVP binding remained detectable during the entire treatment period. Thereafter Bmax was restored to base line values within 2 days of stopping the infusion. These results suggest that d(CH2)5-D-Tyr(Et)VAVP has a high affinity for V2 receptors in both Sprague-Dawley and Brattleboro rats. Its rate of dissociation from the receptor appears to be much slower than that of AVP. In Brattleboro rats, the binding of d(CH2)5-D-Tyr(Et)VAVP leads to an antidiuretic response. In Sprague-Dawley rats, a transient diuretic response is followed by a progressive normalization in water intake. This occurs despite persistent and complete blockade of renal medullary V2 receptors.

• Research Organization: CIBA-GEIGY Limited, Basle (Switzerland)
• OSTI ID: 6681844
• Journal Information: Peptides (Fayetteville, N.Y.); (United States), Vol. 9:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
TUBULES
RECEPTORS
VASOPRESSIN
BIOCHEMICAL REACTION KINETICS
CELL MEMBRANES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ANIMALS
BODY
CELL CONSTITUENTS
HORMONES
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY HORMONES
PROTEINS
REACTION KINETICS
RODENTS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques