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Regulation of the avian kidney by arginine vasotocin.

Nonapeptides secreted by the neurohypophysis have important roles in vertebrate cardio-fluid homeostasis. In birds, those peptides include mesotocin (the representative of the neutral, or oxytocin-like, nonapeptide family) and vasotocin (the representative of the basic, or vasopressin-like, hormones). The function of mesotocin is not well defined, but it does appear to have osmoregulatory functions. Vasotocin is considered the primary avian antidiuretic hormone. Receptors for AVT in avian kidney-either on renal vasculature or on the tubules-have yet to be localized or identified. However, AVT quite certainly effects antidiuresis via both vascular and tubular mechanisms. The former entail a reduction in the rate of glomerular filtration, apparently via constriction of afferent arterioles. Evidence for the latter (direct tubular action of AVT) has accumulated in recent years and includes enhanced fractional tubular water reabsorption, activation of second messenger (cAMP) in thick ascending limbs and collecting ducts, and modest AVT-stimulated water permeability in collecting ducts associated with expression of aquaporins. The relative importance of the renal vascular vs. tubular actions in birds likely depend on the dose of the hormone, the physiological condition of the animal, and the species of bird.

Amino Acid Sequence↗

Evaluation of 1-deamino-[D-Tyr(Oethyl)2, Thr4, Orn8] vasotocin, an oxytocin antagonist, in animal models of uterine contractility and preterm labor: a new tocolytic agent.

We attempted to characterize the ability of a new oxytocin derivative, 1-deamino[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin (ORF 22164), to antagonize the action of oxytocin in several in vitro and in vivo animal models of uterine hyperactivity. In these studies, the derivative was found to be a specific competitive inhibitor of oxytocin-induced contractions of pregnant guinea pig uterus in vitro. In addition, its intravenous administration induced a dose-dependent inhibition of oxytocin-induced uterine contractions in situ. Finally, like ritodrine, the drug induced a dose-dependent delay of ongoing labor in rats. These results suggest that 1-deamino-[D-Tyr(Oethyl)2,Thr4,Orn8] vasotocin, unlike ritodrine, is a potent and specific antagonist of oxytocin-induced uterine contractions and thus may have potential clinical utility in the treatment of preterm labor.

Animals↗

Brain vasotocin pathways and the control of sexual behaviors in the bullfrog.

The neurohypophysial peptide arginine vasotocin (AVT) alters the display of several sexually dimorphic behaviors in the bullfrog (Rana catesbeiana). These behaviors include mate calling, release calling, call phonotaxis, and locomotor activity. Populations of AVT-immunoreactive cells are present in six areas of bullfrog brain and fibers are widespread. Neural areas involved in vocalization, in particular, contain AVT cells and fibers. As well, AVT concentrations in a subset of brain areas are sexually dimorphic and steroid sensitive. Effects of gonadectomy and gonadal steroid treatment vary, depending on the brain area and sex of the frog. For example, some anterior areas are sensitive to changes in both dihydrotestosterone (DHT) and estradiol. In some posterior brain areas, on the other hand, AVT levels are affected only by DHT. A similar situation exists for putative AVT receptors in bullfrogs. Receptors are widespread, occurring in many areas that have been linked to behavior. Receptor concentrations are sexually dimorphic in the amygdala pars lateralis, hypothalamus, pretrigeminal nucleus, and dorsolateral nucleus. Estradiol alters AVT receptor level in the amygdala of both sexes of bullfrog and both estradiol and DHT alter the receptor number in the pretrigeminal nucleus, but only in males. The mechanisms responsible for steroid effects on vasotocin neurons and their targets are unknown. Specific AVT cells, fiber terminal fields, and receptor populations are likely influenced by gonadal steroids for effective timing of individual behaviors displayed by bullfrogs.

Animals↗

Presence of a member of the Tc1-like transposon family from nematodes and Drosophila within the vasotocin gene of a primitive vertebrate, the Pacific hagfish Eptatretus stouti.

Molecular cloning of the vasotocin gene of a cyclostome, the Pacific hagfish Eptatretus stouti, reveals, in contrast to other known members of the vertebrate vasopressin/oxytocin hormone gene family, an unusual exon-intron organization. Although the location of three exons and two introns is conserved, an additional intron is present 5' of the coding region of the hagfish gene. The third intron, which is greater than 14 kilobase pairs in size, contains on the opposite DNA strand to that encoding vasotocin an open reading frame exhibiting striking similarity to the putative transposase of Tc1-like nonretroviral mobile genetic DNA elements, so far reported only from nematodes and Drosophila. The hagfish element, called Tes1, is flanked by inverted terminal repeats representing an example of the existence of a typical inverted terminal-repeat transposon within vertebrates. The presence of Tc1-like elements in nematodes, Drosophila, and cyclostomes indicates that these genetic elements have a much broader phylogenetic distribution than hitherto expected.

Amino Acid Sequence↗

Identification of amino acid residues that direct differential ligand selectivity of mammalian and nonmammalian V1a type receptors for arginine vasopressin and vasotocin. Insights into molecular coevolution of V1a type receptors and their ligands.

Arginine vasotocin (VT) is the ortholog in all nonmammalian vertebrates of arginine vasopressin (AVP) in mammals. We have previously cloned an amphibian V1atype vasotocin receptor (VT1R) that exhibited higher sensitivity for VT than AVP, while the mammalian V1a type receptor (V1aR) responded better to AVP than VT. In the present study, we identified the amino acid residues that confer differential ligand selectivity for AVP and VT between rat V1aR and bullfrog VT1R (bfVT1R). A chimeric rat V1aR having transmembrane domain (TMD) VI to the carboxyl-terminal tail (C-tail) of bfVT1R showed a reverse ligand preference for AVP and VT, whereas a chimeric VT1R with TMD VI to the C-tail of rat V1aR showed a great increase in sensitivity for AVP. A single mutation (Ile(315(6.53)) to Thr) in TMD VI of V1aR increased the sensitivity for VT, while a single mutation (Phe(313(6.51)) to Tyr or Pro(334(7.33)) to Thr) reduced sensitivity toward AVP. Interestingly the triple mutation (Phe(313(6.51)) to Tyr, Ile(6.53) to Thr, and Pro(7.33) to Thr) of V1aR increased sensitivity to VT but greatly reduced sensitivity to AVP, behaving like bfVT1R. Further, like V1aR, a double mutant (Tyr(306(6.51)) to Phe and Thr(327(7.33)) to Pro) of bfVT1R showed an increased sensitivity to AVP. These results suggest that Phe/Tyr(6.51), Ile/Thr(6.53), and Pro/Thr(7.33) are responsible for the differential ligand selectivity between rat V1aR and bfVT1R. This information regarding the molecular interaction of VT/AVP with their receptors may have important implications for the development of novel AVP analogs.

Amino Acid Sequence↗

Effects of phosphate, prostaglandins, arachidonic acid and arginine vasotocin on oviposition and pigment secretion from the shell gland in Japanese quail.

1. Phosphate solution, prostaglandin F2alpha and E2, arachidonic acid and arginine vasotocin were injected intrauterinely or intravenously into laying quail hens 6 h before expected oviposition. Following injections, induced ovipositions and secretions of pigment from their shell glands were observed. 2. The effects of intrauterine injection with prostaglandins, which induced oviposition and pigment secretion, were not inhibited by pre-injection of indomethacin. 3. Indomethacin completely inhibited the inducing effects on oviposition and pigment secretion of intrauterine injections with phosphate solution and arachidonic acid. 4. Intravenous injection with arginine vasotocin or prostaglandins also induced oviposition and pigment secretion; indomethacin, however, only inhibited pigment secretion. 5. It is concluded that the effects of prostaglandins on pigment secretion from the shell gland were demonstrated experimentally.

Animals↗

[Arg8]vasotocin excites neurones in the dorsal vagal complex in vitro: evidence for an action through novel class(es) of CNS receptors.

Using extracellular recordings from brainstem slices in vitro, it was demonstrated that a high proportion (38/56) of neurones in the dorsal vagal complex of dioestrus, virgin female rats exhibit an excitatory response to [Arg8]-vasotocin (AVT). Pharmacological characterization suggests that these responses cannot be entirely explained by interaction with either of the currently known classes of central receptors for oxytocin (OT) and vasopressin (V1a). Comparison of the responses with those to the OT receptor-specific agonist [Thr4,Gly7]-OT (TGOT), showed that not all neurones that responded to TGOT also responded to AVT (3/27). Furthermore, while the effects of 10(-7) M TGOT could be blocked either by the broad-spectrum antagonist d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-vasopressin or by the selective OT receptor antagonist d(CH2)5[Tyr(Me)2,Thr4,Orn8,Tyr-NH2(9)]-vasotocin, these peptides did not completely block the responses to AVT, indicating that AVT is unlikely to act through the central OT receptor. The responses to AVT and [Arg8]-vasopressin (AVP) indicated the presence of at least 2 classes of receptor with which these agonists could act. Of 42 neurones tested with both AVP and AVT, none responded to AVP in the absence of a response to AVT, while 7/42 responded to AVT without a response to AVP. This might be explained by AVP acting through only the V1 receptor, while AVT acts through both the V1 and its own novel class of receptor. This was substantiated by the fact that two OT/V1 receptor antagonists, d(CH2)5[d-Tyr(OEt)2,Val4,Cit8]-VP and d(CH2)5[Tyr(Me)2,Tyr-NH2(9)]-AVP, were unable to block completely all the responses to AVT at a dose which suppressed responses to both AVP and TGOT.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Mesotocin and vasotocin, two neurohypophysial hormones in the ostrich, Struthio camelus.

Two neurohypophysial hormones have been isolated from an avian species, the ostrich, Struthio camelus. Both have been characterized by amino acid analysis and sequence determination. The data obtained suggest that the oxytocin-like hormone is [Ile8-oxytocin] (mesotocin) and the vasopressin-like hormone is [Ile3-vasopressin] (vasotocin). Bioactivity measurements based on urinary conductivity showed vasotocin to be about five times as active as mesotocin.

Amino Acid Sequence↗

Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women.

Three analogues of posterior pituitary hormones, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin(dE-VVT), 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 micrograms/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40-50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 l/h. The bioavailability of 100 ng/kg given intranasally was about 5.5%. Further studies are recommended.

Adult↗

Effects of pineal indoles and arginine vasotocin on lipolysis and lipogenesis in isolated adipocytes.

The effects of arginine vasotocin and the pineal indoles melatonin, serotonin, N-acetylserotonin, hydroxytryptophol, methoxytryptophol, hydroxyindoleacetic acid, methoxyindoleacetic acid, and methoxytryptamine on lipolysis and lipogenesis in isolated adipocytes were studied. Basal lipolysis was inhibited by all the indoles tested at a dose of 1 mumole except hydroxytryptophol. Methoxytryptamine and serotonin inhibited hormone-induced lipolysis in a dose-dependent manner and exhibited the highest antilipolytic activity in isolated rat, rabbit, and hamster adipocytes. However, their antilipolytic activity could not be overcome by increasing the dose of the lipolytic hormone. Dibutyryl cyclic AMP-induced lipolysis was also inhibited. All the pineal indoles tested were capable of suppressing basal and insulin-stimulated lipogenesis in the dose range 0.33-3 nmole. At lower doses there was no effect. Arginine vasotocin at a dose of 25 nmole significantly augmented basal lipogenesis.

Adipose Tissue↗

Influence of age on August levels of pineal immunoreactive arginine vasotocin in rats.

The present study was undertaken to evaluate carefully the influence of age on physiological levels of arginine vasotocin-like peptide in rat pineal glands. Glands were collected from male and female rats aged 13, 33, 53, and 73 days on August 4, 12, and 19, 1984. Individual extracts were assayed for arginine vasotocin (AVT) by radioimmunoassay. The results confirm our previous observation that rat pineal AVT immunoactivity (iAVT) increases significantly during August each year; and in this study, each group of rats reached the same peak level of iAVT (700-750 pg/gland) regardless of age or gender. Thus we do not confirm a previously reported decrease in AVT activity with age. In our studies thus far, season of the year is the physiological variable with the most significant influence on pineal AVT activity levels.

Aging↗

Insulin release from isolated mouse islets in vitro: no effect of physiological levels of melatonin or arginine vasotocin.

Some data in the literature suggest that heightened activity of the pineal gland may be diabetogenic. The onset of insulin-dependent diabetes mellitus is highest during the winter months and at puberty when melatonin levels are also greatest. To study the direct effects of pineal hormones on insulin release, hand-dissected ob/ob-mouse islets of Langerhans were incubated in vitro with melatonin (1 nmol/l to 100 mumol/l) or arginine vasotocin (1 pmol/l to 10 mumol/l) and D-glucose (3 or 20 mmol/l for 1 hr. Melatonin did not affect basal or glucose-stimulated insulin release. Arginine vasotocin (AVT) did not affect basal insulin release, but at presumably pharmacological levels (1 and 10 mumol/l) the peptide significantly increased glucose-stimulated insulin release. We conclude that melatonin and AVT at physiological concentrations have no direct effect on islet insulin release, and that any diabetogenic effect of the pineal gland must occur via suppression of insulin action or via production of a metabolite or hormone that suppresses insulin release.

Animals↗

Pineal vasotocin: release into cat cerebrospinal fluid by melanocyte-stimulating hormone release-inhibiting factor.

The intracarotid injection of both synthetic melanocyte-stimulating hormone release-inhibiting factor (MIF) and purified MIF prepared from bovine hypothalami induces arginine vasotocin release into cerebrospinal fluid of cats and significantly decreases the pineal arginine vasotocin content at 5 minutes after the injection. The present results demonstrate an extrapituitary endocrine effect of synthetic and purified bovine MIF.

Animals↗

Biosynthesis of a vasotocin-like peptide in cell cultures from pineal glands of human fetuses.

Cultured cells from pineal glands of human fetuses release into their media a substance that has antidiuretic and hydroosmotic activities. The ratio of these activities as well as their susceptibility to tryptic digestion, specific oxidative inactivation by tyrosinase, and reductive inactivation by sodium thioglycollate, indicates the presence of a basic peptide, presumably identical with arginine vasotocin. The total amount of this peptide released into the culture media during 38 days of incubation is about ten times greater than the amount contained in nonincubated pineal glands from fetuses of the same age, strongly suggesting that fetal ependymal cells from the pineal gland can synthesize in vitro a peptide similar to arginine vasotocin.

Animals↗

Arginine vasotocin: effects on development of reproductive organs.

Immature 25-day-old mice were injected daily with 1 microgram of arginine vasotocin for 3 or 4 days and killed 24 hours after the last injection. The ovaries were 30 percent smaller in treated females than in controls. The ventral prostates and accessory organs (seminal vesicles and coagulating glands) were less than half the size of these structures in control males. Similar results were observed when 15-day-old mice were given similar injections and killed 2 weeks after the last injection; furthermore, testis weights were 28 percent smaller than those of controls. It is speculated that arginine vasotocin, which has been found in mammalian pineal glands, might mediate effects of the pineal gland on normal sexual development.

Age Factors↗

Neurophysiological effects of vasotocin and corticosterone on medullary neurons: implications for hormonal control of amphibian courtship behavior.

Research on a wide variety of vertebrates, from fish to mammals, reveals that corticosteroid hormones and vasotocin-like neuropeptides can potently modulate reproductive behaviors. But, it is not clear how the behavioral effects of these chemical messengers relate to functional properties of behavior-controlling neurons. This problem was investigated in the roughskin newt, Taricha granulosa, an amphibian in which the administration of arginine vasotocin (AVT) facilitates and corticosterone (CORT) inhibits courtship clasping of females by males. In waking, immobilized male newts, neurophysiological effects of AVT and CORT were studied in neurons in the rostral medulla due to the probable role of these neurons in the control of clasping. Topical medullary application of a clasp-facilitating dose of AVT produced a rapid increase in neuronal responsiveness to pressure on the cloaca, a trigger stimulus for clasping responses. Neuronal responses to noncloacal somatic stimuli and to moving visual stimuli were also enhanced. Systemic CORT administration, which has previously been shown to depress newt medullary neuronal sensory responsiveness, reversed the action of AVT such that the peptide depressed sensory responsiveness when applied 30 min after CORT. When AVT application preceded CORT injection by 10-17 min, however, the usual suppressive CORT effect was reversed and this treatment resulted in a rapidly appearing potentiation of neuronal activity and enhanced somatic sensory responsiveness. If the interval between AVT and CORT was increased to 30 min, the steroid caused a rapid depression of firing and a diminished somatic sensory responsiveness in most neurons, similar to what occurs in newts treated with CORT alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Radioimmunoassay of vasotocin, vasopressin, and oxytocin in human neonatal cerebrospinal and amniotic fluid.

Arginine vasotocin (AVT) has been measured in neonatal cerebrospinal fluid (CSF) and human amniotic fluid using a newly developed specific radioimmunoassay system. There were significant amounts of AVT in all samples. Vasopressin and oxytocin also were measured in the samples and could not account for the levels of vasotocin found. The source and function of these neurohypophyseal peptides in CSF and amniotic fluid remains speculative.

Adult↗