Oxytocin, Vasotocin and Analogs

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Introduction

The peptide oxytocin (OT) belongs to a group of neurohypophysial hormones present in virtually all vertebrates and many other species as primitive as the earthworm Eisenia fetida. The OT family contains a neutral amino acid in position 8, vasopressins a basic amino acid (Arg or Lys). Virtually all vertebrate species possess an OT-like and a VP-like peptide each with a different receptor and a different function. The two neurohypophysial hormones of bony fishes, believed to be predecessors of the land vertebrates, are isotocin (IT) and vasotocin (VT). Oxytocin-like peptides are members of a family of highly related neurohypophyseal nonapeptides that are present in all animals. Arginine⁸-vasotocin (AVT) is the specific peptide that serves antidiuretic and pressor functions in all vertebrate taxa except mammals, most of which produce arginine⁸-vasopressin (AVP) for these functions. These two neuropeptides differ only in that AVP has phenylalanine rather than isoleucine in position 3. In addition to the antidiuretic and pressor effects of these neuropeptides, AVT and AVP appear to act in the vertebrate brain and spinal cord to mediate a diverse array of complex functions, particularly regulation of reproductive behaviors. In addition, neural development and control of cellular responses to neuronal injury may be influenced by vasopressin-like neuropeptides.

Mechanism of action

Many aspects of the oxytocin system including behavioral effects mediated or modulated by oxytocin, physiological regulation by steroids, and the functions of OT-like hormones in nonmammalians are poorly understood. Numerous studies of mammalian and nonmammalian vertebrate species suggest that the neurobehavioral effects of AVT and AVP are mediated by V₁-like receptors in the central nervous system. Agonist activation of G-protein-coupled receptors, such as the receptors mediating AVT and AVP behavioral effects, triggers a cascade of events, including internalization of the ligand-receptor complex. This internalization may modulate cell responsiveness by causing the loss of receptors from the cell surface, making them inaccessible to continued ligand challenge.

Application of Oxytocin

Oxytocin is associated with reproductive functions, the stimulation of uterine contractions during labor and milk ejection during lactation, whereas VT facilitates water reabsorption by the kidney and the contraction of smooth muscle cells in arteries.

References

1. Wyttenbach, T., Liu, D., & Bowers, M. T. (2008). Interactions of the Hormone Oxytocin with Divalent Metal Ions. Journal of the American Chemical Society, 130(18), 5993–6000.
2. Lewis, C. M., Dolence, E. K., Zhang, Z., & Rose, J. D. (2004). Fluorescent Vasotocin Conjugate for Identification of the Target Cells for Brain Actions of Vasotocin. Bioconjugate Chemistry, 15(4), 909–914.