Iodination of vasopressin analogues with agonistic and antagonistic properties: effects on biological properties and affinity for vascular and renal vasopressin receptors.
Twelve L- and D-tyrosine-containing vasopressin analogues were prepared in their mono- and diiodinated forms. These include six arginine vasopressin (AVP) vascular (V1) type antagonists/antidiuretic (V2) agonists, four V1/V2 antagonists, and two V1/V2 agonists, one of which is AVP itself. Ten peptides were iodinated on the tyrosyl residue in position 2; two were iodinated on a tyrosyl amide residue replacing the glycyl amide residue at position 9. All peptides were tested both for their biological activities in vivo (rat vasopressor and antidiuretic tests) and for their ability to bind to vasopressin receptors of the V1 (vascular) and V2 (renal) types from rat liver and rat kidney membranes, respectively. It is shown that monoiodination of the tyrosyl residue in the vasopressin analogues that were tested either preserves or reduces to a highly variable extent the in vivo and in vitro biological activities of these analogues. In most cases diiodonitation resulted in a marked decrease in biological activity. The effects of iodination on the affinity of vasopressin analogues for hepatic V1 receptors and renal V2 receptors were more related to the affinity of the noniodinated peptide for these receptors than to the biological properties (antagonist versus agonist) of the tested analogues, the nature (L versus D) of the iodinated tyrosyl residue, or the position (2 versus 9) at which this residue was introduced. The loss of affinity due to iodination was usually more pronounced for peptides exhibiting high affinity for vasopressin receptors. However, we show that among the monoiodinated peptides some (especially monoiodinated [2-D-Tyrosine]-AVP) retained enough affinity for vasopressin binding sites to suggest that their radioiodinated conterparts would be promising labeled ligands for use in studies in vasopressin receptors.
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007455:Iodine / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017483:Receptors, Vasopressin; D013056:Spectrophotometry, Ultraviolet; D014662:Vasoconstrictor Agents / Q000378:metabolism; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology
D010455:Peptides; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D001127:Arginine Vasopressin; D007455:Iodine