Surprising pharmacological activity of analogues designed by substitution of position 3 in arginine vasopressin (AVP) and 8-D-arginine vasopressin with L-2-napthylalanine.
In an attempt to develop more active and selective analogues of arginine vasopressin (AVP), two peptides have been designed, synthesized and tested for vasopressor (V1-receptors) and antidiuretic (V2-receptors) activities. We also estimated the uterotonic and anti-uterotonic activities of these compounds in-vitro. The first peptide, [(L-2-Nal)3] AVP is a highly active V2-agonist. The second analogue, [(L-2-Nal)3, (D-Arg)R]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first V1-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.
Lammek
B
B
Faculty of Chemistry, University of Gdansk, Poland.
Konieczna
E
E
Trzeciak
H I
HI
Kozłowski
A
A
Szymkowiak
J
J
Stojko
R
R
Kupryszewski
G
G
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects
D017483:Receptors, Vasopressin; C103278:arginine vasopressin, 2-naphthylalanine(3)-; D001127:Arginine Vasopressin