Vasopressin Related Peptides、加壓素相關(guān)肽

Definition

Vasopressin is best known for its antidiuretic and vasopressor actions, but the hormone also exerts potent hepatic effects. There are seven vasopressin-like peptides that activate hepatic glycogen phosphorylase and stimulate phosphate incorporation into phosphatidylinositol.

Discovery

In 1977 Hems et al., studied stimulation of gluconeogenesis and glycogenolysis, and inhibition of fatty acid synthesis by vasopressin. Cyclic nucleotides are not implicated in the mechanism whereby vasopressin exerts these effects , but a role for Ca2+ mobilization in the cytosol has been suggested 1,2. Related neuropeptides include oxytocin (OT) in mammals and isotocin and vasotocin in other vertebrates. The divergence of arginine vasopressin (AVP) and OT appears to have occurred early in the vertebrate lineage. In invertebrates, similar peptides have been described in the earthworm 3.

Structural Characteristics

The vasopressins are nonapeptides. The primary amino acid sequence of arginine vasopressin is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly and for lysine vasopressin, lysine is present in place of the arginine.  AVP is a highly conserved nonapeptide. Proux et al. identified the presence of two isoforms of the peptide, a monomeric form (F1), and an antiparallel homodimer (F2) in locust ganglia, but not a parallel homodimer (D2). Of the three isoforms of AVP, F2 was found to be the most active for increasing the secretion of locust MT. However, the finding of diuretic activity of F2 and F1 was not confirmed in an independent investigation4.

Mode of Action

Christopher et al., have shown that the Ca2+-dependent glycogen breakdown induced by vasopressin in hepatocytes is associated with a marked stimulation of Pi incorporation into phosphatidylinositol, which is largely Ca2+ independent. Billah & Michell in 1978 have confirmed this observation and shown that vasopressin also stimulates the Ca2+ independent breakdown of phosphatidylinositol in hepatocytes. Michell et al. in 1977 have suggested that ligand-stimulated phosphatidylinositol breakdown in a variety of tissues is involved in the coupling between receptor-agonist interactions and enhanced Ca2+-mobilization in the cytosol. Results described the relationship between the concentration-dependence of glycogen phosphorylase activation and that of stimulated phosphatidylinositol metabolism in hepatocytes exposed to various neurohypophyseal hormones and related analogues 5. Administration of pharmacological doses of arginine-vasopressin, related peptides, and other pressor agents induced a profound release of atriopeptin immunoreactivity into the circulation. The stimulated release of atriopeptin apparently was related to increased arterial blood pressure. Neither the nonpressor vasopressin analog 1-deamino-D-Arg8-vasopressin nor arginine-vasopressin in the presence of a specific pressor antagonist caused atriopeptin to be released into the circulation. Urine output was correlated with the level of atriopeptin released. Physiological levels of arginine-vasopressin suppress diuresis and produced vasoconstriction 6.   

Functions

Diuresis and vasodilation, pharmacological levels of the hormone stimulated the cardiac endocrine system to release atriopeptin, which may cause diuresis and vasodilation to physiologically antagonize the effects of vasopressin 6.   

Hippocampal Corticosterone Receptor, vasopressin-related peptides increase the hippocampal corticosterone receptor capacity of diabetes insipidus (Brattleboro) rats 7.

Vasopressin (VP)/oxytocin (OT)-related peptides constitute a large superfamily found in a wide range of both vertebrate and invertebrate species. While intensive literature reports that these neuropeptides influence behavior, especially learning and memory, in numerous species from diverse vertebrate groups, their roles in behavioral regulation have never been studied in invertebrates.

Congenitally lacking vasopressin, the aged rat shows a decline in hippocampal corticosterone receptors and dysfunction in learning and adrenocortical physiology previously linked to glucocorticoid effects upon the hippocampus. The Brattleboro rat, congenitally lacking vasopressin, also has a low number of hippocampal glucocorticoid receptors, as well as learning and endocrine impairments similar to those seen in the aged.

References

1.Hems DA (1977). Short-term hormonal control of hepatic carbohydrate and lipid catabolism. FEBS Lett., 80(2): 37-245.

2.Chen JL, Babcock DF, Lardy HA (1978). Norepinephrine, vasopressin, glucagon, and A23187 induce efflux of calcium from an exchangeable pool in isolated rat hepatocytes. PNAS., 75(5): 2234-2238.

3.Takuwa-Kuroda K, Iwakoshi-Ukena E, Kanda A, Minakata H (2003). Octopus, which owns the most advanced brain in invertebrates, has two members of vasopressin/oxytocin superfamily as in vertebrates. Regul. Pept., 115:139-149.

4.Proux JP, Herault JP (1988). Cyclic AMP: a second messenger of the newly characterized AVP-like insect diuretic hormone, the migratory locust diuretic hormone. Neuropeptides, 12:7-12.

5.Kirk CJ, Verrinder TR, Hems DA (1978). The influence of extracellular calcium concentration on the vasopressin-stimulated incorporation of inorganic phosphate into phosphatidylinositol in hepatocyte suspensions. Biochem. Soc. Trans., 6(5):1031-1033.

6.Manning PT, Schwartz D, Katsube NC, Holmberg SW, Needleman P (1985). Vasopressin-stimulated release of atriopeptin: endocrine antagonists in fluid homeostasis. Science, 229(4711):395-397.

7.Veldhuis HD, de Kloet ER (1982). Vasopressin-related peptides increase the hippocampal corticosterone receptor capacity of diabetes insipidus (Brattleboro) rats.  Endocrinology, 110(1):153-157.