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Evaluation of the pharmacologic properties of a vasopressin antagonist in Brattleboro rats

Mah, S. C. and Hofbauer, K. G.. (1988) Evaluation of the pharmacologic properties of a vasopressin antagonist in Brattleboro rats. The Journal of Pharmacology and Experimental Therapeutics, Vol. 245, H. 3. S. 1028-1032.

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Official URL: http://edoc.unibas.ch/dok/A5258634

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Abstract

The arginine vasopressin (AVP) analog d-(CH2)5-D-Tyr(Et)VAVP is a potent competitive antagonist of AVP at renal tubular AVP receptors. In Sprague-Dawley rats, this compound induces diuresis after single injections but only a transient diabetes insipidus-like state during continuous infusion. To further evaluate the pharmacologic profile of d-(CH2)5-D-Tyr(Et)VAVP, the present experiments were performed in Brattleboro rats homozygous for hereditary hypothalamic diabetes insipidus. In these rats, acute and chronic administration of the antagonist induced significant antidiuretic effects. These agonistic effects persisted for up to 4 days after single injections and for more than 2 weeks after stopping continuous infusions. The antidiuretic effects of the antagonist during chronic administration were indistinguishable from those of AVP replacement. When the renal tubular AVP receptor antagonist was infused into diabetes insipidus rats that had received AVP for 1 week, it induced a transient rise in water intake. However, the peak values after administration of the antagonist were much lower than after AVP withdrawal. These observations suggest that d-(CH2)5-D-Tyr(Et)VAVP has substantial agonistic properties that are not detectable in Sprague-Dawley rats except for limiting the compound's maximum anti-antidiuretic efficacy. These agonistic effects together with endogenous compensatory mechanisms may allow Sprague-Dawley rats to maintain a normal water balance during the continuous administration of d-(CH2)5-D-Tyr(Et)VAVP.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Pharmacology/Neurobiology (Hofbauer)
UniBasel Contributors:Hofbauer, Karl G.
Item Type:Article, refereed
Bibsysno:Link to catalogue
Publisher:Williams and Wilkins
ISSN:0022-3565
Note:Publication type according to Uni Basel Research Database: Journal article
Last Modified:22 Mar 2012 14:22
Deposited On:22 Mar 2012 13:31

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