Vasotocin

Discovery

Vasotocin was chemically synthesized in 1958 as an analog of neurohypophysial hormones containing a ring of oxytocin (OT) and a side chain of vasopressin (VP). Subsequently, VT has been isolated from various vertebrate species. All nonmammalian vertebrates have VT as a VP family peptide. Because cyclostomes contain only VT, the VT gene is considered to be an ancestral gene for all vertebrate neurohypophysial hormones.

Structure

The intramolecular ring structure is identical to that of OT while the eighth aa residue in the C-terminal extension is arginine. Therefore, VT is a basic VP family peptide. The C-terminus of VT is amidated. In anuran amphibians, two types of C-terminally extended peptides called hydrins have been found. Mr 1050. VT is freely soluble in water, with increased stability under acidic conditions using acetic acid.

Gene, mRNA, and precursor

From cartilaginous fish to birds, the VT gene is located on the same chromosome with the respective OT-family genes in a tail-to-head orientation. The existence of cis-regulatory elements that mediate neuron-specific expression was suggested for the pufferfish fugu. Similar to VP precursors, VT precursors are composed of a signal peptide, a mature peptide, processing and amidation motifs, neurophysin, and copeptin moieties. The copeptins of tetrapods and cartilaginous fish are considered to be glycopeptides while no glycosylation site is found in teleosts and cyclostomes.

Receptors

Currently, four specific receptors have been identified in nonmammalian vertebrates. Of these, V2bR (further subdivided to V2b,c,dR; see “Neurohypophysial hormone family”) is a newly discovered receptor and is either a pseudogene or has disappeared in mammals while the other three receptors (V1aR, V1bR, and V2aR) are orthologous to mammalian VP receptors. Specifically, only in birds, VT receptors have been named differently as VT1R (V2bR), VT2R (V1bR), VT3R (mesotocin receptor, MTR), and VT4R (V1aR). V2aR has not been found in birds and cartilaginous fish while the existence of V1bR in teleosts has not been proven. In teleosts, further duplications of receptors have been found.  Similar to mammalian VP receptors, V1aR and V1bR couple to Ca2+ signaling pathways while V2aR couples to the adenylate cyclase pathway. V2bRs, including chicken VT1R, are structurally related to the conventional V2 receptor (V2aR), but couple to Ca2+ signaling pathways.

Agonist and antagonists

Only a few studies have tested the selectivity and potency of agonists and antagonists to the nonmammalian receptors. The following antagonists for mammalian receptors have been used: V1a antagonists, OPC-21268, SR-49059, d(CH2)5[Tyr(Me)2 ]AVP (Manning compound); V1b antagonist, SSR-149415; V2a antagonists: OPC-31260, d(CH2)5[D-Ile2 ,Ile4 ,Ala-NH2]AVP.

Synthesis and release

In birds, the synthesis and release of VT are increased by water deprivation, drinking hypertonic saline, and hemorrhage. The involvement of a transcription factor, TonEBP, is implicated in enhanced VT synthesis after salt loading. Osmotic manipulation increases the synthesis and release of VT in reptiles, amphibians, many teleosts, and sharks. In birds, plasma VT levels transiently increase at the time of oviposition and decrease within 30min after egg laying, which is correlated with increases in uterine contractility. Direct and indirect regulation of VT synthesis by androgen and estrogen is shown in the sexually dimorphic BNST and amygdala. VT release from the neurohypophysis is stimulated by steroid hormones and other hormones, including angiotensin II and urotensin I. Brain VT content is high in aggressive stickleback males that take care of eggs.

Biological functions

VT is important for osmoregulation and ionoregulation in vertebrate groups from fish to birds. The antidiuretic effect is particularly important in terrestrial species. VT is also implicated in cardiovascular and glycogenolytic effects, circadian and seasonal biology, uterine contraction, stress response, and social and reproductive behaviors.

Description

VT is a vasopressin-family peptide of all nonmammalian vertebrates; roles in body fluid homeostasis, reproduction, behavior, and stress response have been implicated.

Raw materials

Preparation Products