[3H]AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin.
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.
Cardiovascular Research Department, CIBA-GEIGY Limited, Basle, Switzerland.
S C
SC
Mah
S E
SE
Whitebread
M
M
De Gasparo
K G
KG
Hofbauer
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D017483:Receptors, Vasopressin; D012016:Reference Values; D014316:Tritium; D014667:Vasopressins / Q000037:antagonists & inhibitors*
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014316:Tritium; D014667:Vasopressins; D001127:Arginine Vasopressin; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin