Vasopressin, biological activity

These include nicotinic acetylcholine receptors, neuronal calcium channels, muscle sodium channels, vasopressin receptors, and iV-methyl-D-aspartate (NMDA) receptors. Some general features of the structure, function, and evolution of biologically active peptides isolated from Conus venom are presented. 

R. J. Turner, J. M. Matsoukas, and G. J. Moore, Tyrosinate fluorescence lifetimes for oxytocin and vasopressin in receptor-simulating environments Relationship to biological activity and H-NMR data, Biochem. Biophys. Res. Commun. 171, 996-1001 (1990). 

Many biologically active secreted peptides are also amidated at their carboxyl terminal, and acetylated at their amino-terminal. The consequences of these modifications are (a) to reduce the susceptibility of these peptides to degradative actions of extracellular aminopeptidases and carboxypeptidases after their secretion and (b) to influence the biological activity of the peptides. Corticotropin-releasing factor, gastrin, cholecystokinin and vasopressin require the C-terminal amide for full activity [54—56]. Acetylation of the N-terminus of a-MSH is necessary for activity, whereas acetylation of /3-endorphin inhibits its opioid activity [57], The enzymes responsible for acetylation have been identified from bovine and rat intermediate lobes [57] and enzymes with a-amidation activity have been reported in preparations of pituitary secretory granules [54,55]. 

Also, prolylendopeptidase inhibitory peptides (PEP) have been found in wines (Yanai et al. 2003). PEP may have a role in the degradation of biologically active peptides containing proline, such as oxytocin, vasopressin, substance P, bradykinin, neurotensins and angiotensins. Two inhibitory peptides have been isolated and characterized, Pep A (Val-Glu-Ile-Pro-Glu) and Pep B (Tyr, Pro, He, Pro, Phe). Both of them showed PEP inhibition, thereby suppressing the degradation of neuropeptides, vasopressin, substance P and fragments 8-13 of neurotensin, which are involved in memory and neural communication. 

Slaninova, J., Machova, A., Kuncarova, P., Maletinska, L., and Howl, J. (2001) Receptor affinity and biological activity of chimeric peptides combining bradykinin with arginine vasopressin of fibronectin-related RGD sequences, in 2nd Hellenic Forum on Bioactive Peptides (Cordopatis, P. A. ed.), Typorama, Patras, pp. 359-365. 

Vasopressin is rapidly cleared from the circulation and must be given by continuous i.v. infusion. The synthetic ancJogue, terlipressin (triglycyl-lysine-vasopressin) is now preferred. This prodrug (or hormogen) is converted in vivo to the vasoactive lysine vasopressin which has biological activity for 3-4 hours, and is effective by bolus injections 4-hourly, usually for 48-72 hours. It is a useful adjunct to endoscopic therapy and reduces rebleeding. 

Advantages of the solid-phase method are amenability to automation, the almost 100% yield of product for each reaction, the ease of removal of excess reagents and waste products by washing and filtration of resin particles, the lack of need for purification of intermediates, and speed. Peptides or proteins that have been synthesized by the solid-phase method include ribonuclease, bradykinin, oxytocin, vasopressin, somatostatin, insulin, and the S-chain of hemoglobin. The sequence analyses for these substances were confirmed by demonstrating that the synthetic products, constructed on the basis of sequence data, had the same biological activities as those of the corresponding natural substances. 

Vasopressin - Examination of possible conformational features of arginine vasopressin (AVP) led Walter et al. to propose a biologically active conformation" for vasopressin at the kidney antidiuretic receptor. The key residues for receptor binding were postulated to be the lipophilic side chains of Phe , Gln, Pro, and Arg in vasopressin (H-Cy,s-Tyr-Phe-Gln-Asn-Cy s-Pro-Arg-Gly-NH2), while the key "active elements" for trans-... 

The ONP method has been used by Hruby and colleagues in a synthesis of the 20-membered cyclic disulfide designated tocinoic acid which encompasses the tocin ring of oxytocin. In addition to the oxytocin-(1-6)-hexapeptide amide the vasopressin-(1-6)-hexapeptide (Chart 6) amide has also been recently synthesized. In terms of biological activity the conclusion was reached that the tripeptide side chain of the naturally occurring nonapeptide hormones is necessary for the pressor effects as neither amide showed any influence on the despinalized rat blood pressure. Otherwise, both exhibit some of the usual oxytocin and vasopressin activity. 

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