PT  - JOURNAL ARTICLE
AU  - C F Uyehara
AU  - S Caltabiano
AU  - L B Kinter
AU  - M Gellai
TI  - Noncyclic vasopressin analogs are effective diuretics in conscious rats.
DP  - 1989 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1128--1133
VI  - 251
IP  - 3
4099  - http://jpet.aspetjournals.org/content/251/3/1128.short
4100  - http://jpet.aspetjournals.org/content/251/3/1128.full
SO  - J Pharmacol Exp Ther1989 Dec 01; 251
AB  - Linear vasopressin analogs lacking a cyclic hexapeptide ring have recently been reported to possess vasopressin antagonist activity. In conscious, chronically catheterized, euhydrated Sprague-Dawley rats, we have compared the effects of two noncyclic vasopressin analogs, peptide 1 ([1-admantaneacetic acid,2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9-arg]arginine vasopressin) and peptide 2 ([1-propionic acid, 2-(O-ethyl)-D-tyr,4-val,6-(2-aminobutyric acid),9- arg]arginine vasopressin), with a cyclic arginine vasopressin antagonist (SK&F 105494; [1-des cysteine, cyclo(2-O-ethyl-D-tyrosine,6-L-(2-amino-6,6-cyclopentamethylene suberic acid], 4-valine,7-arginine,8-D-arginine, 9-des glycine]-vasopressin). All three analogs caused a dose-dependent increase in urine flow by increasing free-water clearance without significantly changing osmotic clearance or sodium excretion, indicating true functional vasopressin antagonism. Peptides 1 and 2 were as efficacious in inducing a diuresis as SK&F 105494. The order of diuretic potency among the three analogs in vivo was the same as the order of potency determined by in vitro binding to rat renal membrane homogenates, suggesting that the analogs exerted their diuretic effect by acting at renal vasopressin receptors. Thus, noncyclic vasopressin analogs, which are easier to synthesize then cyclic structures, could provide new strategies in the design of drugs for the treatment of water balance disorders.