Hydroosmotic activities of arginine-vasopressins modified either in positions 1, 2 and 4 or at N-terminal extensions.
Vasopressin and its synthetic analogs were studied for their effect on transepithelial water flux in frog urinary bladder. As compared with AVP, 1-deamino-8-D-arginine vasopressin (dDAVP) was about 40 times less effective in stimulating osmotic water flow. The vasopressin analogs obtained by modification in positions 1 and 2 were: [1-(1-mercapto-4-tert-butylcyclohexaneacetic acid)] AVP (I); [1-(1-mercapto-4-methylcyclohexaneacetic acid)]AVP (II); [1-(1-mercapto-4-methylcyclohexaneacetic acid)-2-O-methyltyrosine]AVP (III); and those modified in position 4 were: [1-(1-mercaptocyclohexaneacetic acid)-4-arginine] AVP (IV); [1-(2-mercaptopropionic acid)-4-arginine]AVP (V). Any of the above analogs did not influence basal, but antagonized vasopressin-stimulated water flux. N-terminally extended analogs of AVP: Ala-AVP (VI); Ser-Ala-AVP (VII) and Thr-Ser-Ala-AVP (VIII) stimulated osmotic water flux to the same extent in concentration 200 times higher as that of AVP. We conclude from these studies that vasopressin analogs (I-V) competitively antagonize vasopressin-stimulated hydroosmotic activity in frog urinary bladder probably at the epithelial vasotocin V1 and/or V2 receptor site. N-terminal extension of the vasopressin molecule did not influence the capacity of AVP to induce V2 receptor-mediated action, even when used at higher concentrations.
Bakos
P
P
Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava.
Shakhmatova
E I
EI
Ponec
J
J
Alexandrová
M
M
Lichardus
B
B
Lammek
B
B
Rekowski
P
P
Kupryszewski
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D009995:Osmosis / Q000187:drug effects*; D011896:Rana temporaria; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D017483:Receptors, Vasopressin; D013329:Structure-Activity Relationship; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D014668:Vasotocin / Q000378:metabolism; D014867:Water / Q000378:metabolism
D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; C034862:vasotocin receptor; D014867:Water; D001127:Arginine Vasopressin; D003894:Deamino Arginine Vasopressin; D014668:Vasotocin