Transport Of Oxytocin Research Articles

Oxytocin Dynamics in the Body and Brain Regulated by the Receptor for Advanced Glycation End-Products, CD38, CD157, and Nicotinamide Riboside.

Investigating the neurocircuit and synaptic sites of action of oxytocin (OT) in the brain is critical to the role of OT in social memory and behavior. To the same degree, it is important to understand how OT is transported to the brain from the peripheral circulation. To date, of these, many studies provide evidence that CD38, CD157, and receptor for advanced glycation end-products (RAGE) act as regulators of OT concentrations in the brain and blood. It has been shown that RAGE facilitates the uptake of OT in mother’s milk from the digestive tract to the cell surface of intestinal epithelial cells to the body fluid and subsequently into circulation in male mice. RAGE has been shown to recruit circulatory OT into the brain from blood at the endothelial cell surface of neurovascular units. Therefore, it can be said that extracellular OT concentrations in the brain (hypothalamus) could be determined by the transport of OT by RAGE from the circulation and release of OT from oxytocinergic neurons by CD38 and CD157 in mice. In addition, it has recently been found that gavage application of a precursor of nicotinamide adenine dinucleotide, nicotinamide riboside, for 12 days can increase brain OT in mice. Here, we review the evaluation of the new concept that RAGE is involved in the regulation of OT dynamics at the interface between the brain, blood, and intestine in the living body, mainly by summarizing our recent results due to the limited number of publications on related topics. And we also review other possible routes of OT recruitment to the brain.

Targeted reduction of oxytocin expression provides insights into its physiological roles.

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 hours without milk in their stomachs. OT injection into the dams or rescue with the rat OT gene restores the milk ejection in response to suckling. OT is also needed for post-partum alveolar proliferation. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. Furthermore, homozygous mutant mice show reduced aggression in some tests.

Deficiency in Mouse Oxytocin Prevents Milk Ejection,but not Fertility or Parturition

Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in various behaviors, such as mating and maternal, and memory. To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT. The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary. Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk injection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk injection, but not for mating, parturition and milk production, in mice.

Human placental transport of oxytocin

Human placental transport of oxytocin

Crosstalk in the magnocellular system during osmotic stimulation of one supraoptic nucleus

Neural connections linking the four magnocellular nuclei i.e.,. the paired supraoptic (SON) and paraventricular (PVN) nuclei, may contribute to the simultaneous and parallel changes in firing patterns of oxytocinergic neurons during reflex milk ejection. To investigate these neural connections in the absence of suckling, intranuclear release of oxytocin (OT) was stimulated by microdialysis of hypertonic CSF containing 1 M NaCl (HS-CSF) into the right SON area and glucose metabolism of both SONs and PVNs and the neural lobe of virgin and lactating (10–12 day) rats was mapped by the autoradiographic [ 14C]deoxyglucose (DG) method. OT in the microdialysates and in plasma, obtained before and after 80–90 min of dialysis with CSF or HS-CSF, was quantified by RIA. In both virgin and lactating rats, microdialysis of HS-CSF unilaterally into the SON area significantly ( p < 0.05) increased release of OT in the nucleus and into plasma, which was associated with enhanced ( p < 0.05) metabolic activity in the ipsilateral and contralateral SON and the neural lobe but not in either PVN. Compared with virgins, lactating rats were less active, had lower ( p < 0.05) glucose utilization in the hypothalamo-neurohypophysial system, and less ( p < 0.05) OT in plasma during microdialysis of HS-CSF into the SON area. The osmotic stimulus did not activate neural structures (suprachiasmatic and medial amygdaloid nuclei) near the SON in either hemisphere. Thus, neural connections or, less likely, transport of OT via the subarachnoid space, may function to recruit activation of cells in the contralateral SON following hypertonic stimulation of cells in the other SON.

Fetal to maternal transport of oxytocin across the dual perfused human placenta

Fetal to maternal transport of oxytocin across the dual perfused human placenta

In vivo biosynthesis and transport of oxytocin, vasopressin and neurophysin from the hypothalamus to the spinal cord

The biosynthesis of oxytocin, vasopressin and their associated neurophysins were studied in the projection from the paraventricular nucleus of the hypothalamus to the spinal cord in individual freely-moving adult male rats. Neuropeptide biosynthesis was studied in vivo by the delivery of [ 35S]cysteine through stereotaxically implanted indwelling cannulae using an osmotic minipump delivery system. Following the appropriate chase times, the neural lobe and spinal cord segments T 1-T 4., and T 12-L 2 were removed from fresh tissue; in addition, the nucleus of the solitary tract was punched from frozen coronal sections. The radiolabeled peptides were purified from the tissue homogenates by sequential linear and exponential gradient elution from reverse-phase high performance liquid chromatography columns. This approach has allowed us to purify radiolabeled oxytocin and vasopressin from both the upper and lower spinal cord. However, the kinetics of oxytocin and vasopressin biosynthesis appeared to be remarkably different, as judged by their differential labeling with different pulse and chase times. Additionally, the use of different chase periods following the pulse of radiolabel has allowed us to determine that oxytocin reaches the spinal cord via the fast component of axonal transport (> 8 mm h −1). Using immunoprecipitation and purification by high performance liquid chromatography, we were also able to purify radiolabeled neurophysins from spinal cord tissue homogenates. These results lend further support to a role for oxytocin and vasopressin in the modulation of autonomic nervous system function and to the role of the paraventricular nucleus as an integration center for endocrine and autonomic function.

Biochemistry of peptide-secreting neurons.

Biochemistry of peptide-secreting neurons.J D White, K D Stewart, J E Krause, and J F McKelvyJ D WhiteSearch for more papers by this author, K D StewartSearch for more papers by this author, J E KrauseSearch for more papers by this author, and J F McKelvySearch for more papers by this authorPublished Online:01 Jul 1985https://doi.org/10.1152/physrev.1985.65.3.553MoreSectionsPDF (9 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByRole of perivascular nerve and sensory neurotransmitter dysfunction in inflammatory bowel diseaseCharles E. Norton, Elizabeth A. Grunz-Borgmann, Marcia L. Hart, Benjamin W. Jones, Craig L. Franklin, and Erika M. Boerman22 April 2021 | American Journal of Physiology-Heart and Circulatory Physiology, Vol. 320, No. 5Divergent profile between hypothalamic and plasmatic aminopeptidase activities in WKY and SHR. Influence of beta-adrenergic blockadeLife Sciences, Vol. 192Role of neuron soma firing in the restoration of neurotensin store in sympathetic preganglionic neuron terminals after stimulus-evoked depletionBrain Research, Vol. 640, No. 1-2Peptides in the limbic system: Neurochemical codes for co-ordinated adaptive responses to behavioural and physiological demandProgress in Neurobiology, Vol. 41, No. 6Dynamics of large dense-cored vesicles in synaptic boutons of the cat superior cervical ganglionNeuroscience, Vol. 55, No. 4Use-dependent fade and two-rate recovery of a naloxone-sensitive inhibition in the cat superior cervical ganglionBrain Research, Vol. 611, No. 2Veratridine evokes release of calcitonin gene-related peptide from capsaicin-sensitive nerves of rat urinary bladderEuropean Journal of Pharmacology, Vol. 212, No. 2-3Dynamics of neurotensin stores in the stellate ganglion of the catBrain Research, Vol. 562, No. 2Central actions of CRF on thermogenesis are mediated by pro-opiomelanocortin productsBrain Research, Vol. 541, No. 1Regulated release of multiple peptides from the bag cell neurons ofAplysia californicaBrain Research, Vol. 521, No. 1-2Acetylation alters the feeding response to MSH and beta-endorphinBrain Research Bulletin, Vol. 23, No. 3Novel autonomic neurotransmitters and intestinal functionPharmacology & Therapeutics, Vol. 40, No. 3Rapid release of substance P and LH-RH from synaptosomes prepared from the medial basal hypothalamus and substantia nigraPeptides, Vol. 10, No. 1The coexistence of neuropeptides in feline sensory neuronsNeuroscience, Vol. 27, No. 3The bradykinin-induced release of substance P from nerve fibre endings in the rat saphenous nerve neuroma is not related to electrophysiological excitationNeuroscience Letters, Vol. 92, No. 1Somatostatin(14) and -(28) but not somatostatin(1–12) hyperpolarize CA1 pyramidal neurons in vitroBrain Research, Vol. 448, No. 1Interactions between cholinergic and peptidergic systems in the cerebral cortex and hippocampusProgress in Neurobiology, Vol. 31, No. 2Regional distribution of in vitro release of thyrotropin releasing hormone in rat brainPeptides, Vol. 8, No. 2In vivo biosynthesis and transport of oxytocin, vasopressin and neurophysin from the hypothalamus to the spinal cordNeuroscience, Vol. 17, No. 1 More from this issue > Volume 65Issue 3July 1985Pages 553-606 Copyright & PermissionsCopyright © 1985 by American Physiological Societyhttps://doi.org/10.1152/physrev.1985.65.3.553PubMed2861611History Published online 1 July 1985 Published in print 1 July 1985 Metrics

In vivo biosynthesis and transport of oxytocin, vasopressin, and neurophysins to posterior pituitary and nucleus of the solitary tract

A growing body of literature suggests that oxytocin (OXY) and arginine-vasopressin (AVP), in addition to their neuroendocrine roles, may serve as neuromodulators within the central nervous system of mammals. The present study investigated the biosynthesis of OXY, AVP, and their associated neurophysins in the paraventricular nucleus of the hypothalamus (PVN) and the transport of these peptides to the neural lobe and the nucleus of the solitary tract (NTS) in the brainstem of the rat. Rats were cannulated bilaterally in the PVN, and 24 hr later a 2-hr pulse of [35S]cysteine was administered using an Alzet minipump delivery system. After a 10-hr chase period, the neural lobe was removed and the PVN and NTS were punched. Tissue homogenates were adsorbed to and eluted from octadecyl-silica cartridges and analyzed by linear high performance liquid chromatography (HPLC) gradient elution, chemical and enzymatic modification, and exponential gradient HPLC elution followed by linear HPLC gradient analysis using an ion-pairing buffer system. This rigorous approach has allowed us to identify 35S-labeled material which co-purifies with OXY and AVP from the PVN, neural lobe, and NTS samples. Specific transport of the nonapeptides to the NTS was demonstrated when a unilateral transection of the hypothalamic fibers resulted in a unilateral depletion of the radiolabeled peptides from the NTS samples. Additionally, each of the neurophysins was purified from the neural lobe and NTS samples after linear HPLC gradient analysis, ion-pairing buffer linear gradient analysis, then tryptic digestion followed by exponential gradient HPLC analysis.(ABSTRACT TRUNCATED AT 250 WORDS)