Anovulatory effect of synthetic analogs of arginine vasotocin in the rat.
We synthesized a series of analogs of arginine vasotocin by systematically substituting each residue, and we then evaluated the anovulatory activity of these compounds in the rat, investigating the correlation between molecular structure and anovulatory, pressor, and antidiuretic activities. Substitution of the N-terminus cysteine with 3-mercaptopropanoic acid in arginine vasotocin and arginine vasopressin produced a 3- to 4-fold increase in both anovulatory and antidiuretic activity and only a 10% change in pressor activity. A similar substitution with lysine vasopressin produced no significant change in either anovulatory or antidiuretic potency; however, the pressor activity was reduced by half. Substitution of this cysteine in arginine vasotocin with 2-hydroxy-3-mercaptopropanoic acid produced an analog more potent in anovulatory activity than arginine vasotocin but less potent than [1-(3-mercaptopropanoic acid)]-arginine vasotocin. The most potent anovulatory analog synthesized was [1-(3-mercaptopropanoic acid)]-8-ornithine vasotocin, which gave a 10-fold increase in anovulatory activity, a 4-fold reduction in antidiuretic activity, and only a 10% increase in pressor potency when compared with arginine vasotocin. These data suggest that different receptors are involved in the anovulatory and antidiuretic responses, but that the anovulatory and pressor effects may be mediated through similar receptors. Further work is necessary to produce a peptide that possesses specific anovulatory activity.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D001127:Arginine Vasopressin; D014668:Vasotocin