scholarly journals Blockade of NK3R signaling in the PVN decreases vasopressin and oxytocin release and c-Fos expression in the magnocellular neurons in response to hypotension

2008 ◽  
Vol 295 (4) ◽  
pp. R1158-R1167 ◽  
Author(s):  
Gwendolen E. Haley ◽  
Francis W. Flynn
Keyword(s):  
Intravenous Injection ◽  
Critical Role ◽  
Magnocellular Neurons ◽  
Induced Hypotension ◽  
Blood Samples ◽  
Oxytocin Release ◽  
Fos Expression ◽  
Plasma Hormone ◽  
Neurokinin 3 Receptor ◽  
Broad Role

Tachykinin neurokinin 3 receptor (NK3R) signaling has a broad role in vasopressin (VP) and oxytocin (OT) release. Hydralazine (HDZ)-induced hypotension activates NK3R expressed by magnocellular neurons, increases plasma VP and OT levels, and induces c-Fos expression in VP and OT neurons. Intraventricular pretreatment with the specific NK3R antagonist, SB-222200, eliminates the HDZ-stimulated VP and OT release. NK3R are distributed in the central pathways conveying hypotension information to the magnocellular neurons, and the NK3R antagonist could act anywhere in the pathways. Alternatively, the antagonist could act at the NK3R expressed by the magnocellular neurons. To determine whether blockade of NK3R on magnocellular neurons impairs VP and OT release to HDZ, rats were pretreated with a unilateral PVN injection of 0.15 M NaCl or SB-222200 prior to an intravenous injection of 0.15 M NaCl or HDZ. Blood samples were taken, and brains were processed for VP/c-Fos and OT/c-Fos immunohistochemistry. Intravenous injection of 0.15 M NaCl did not alter plasma hormone levels, and little c-Fos immunoreactivity was present in the PVN. Conversely, intravenous injection of HDZ increased plasma VP and OT levels and c-Fos expression in VP and OT magnocellular neurons. Intra-PVN injection of SB-222200 prior to an intravenous injection of HDZ significantly decreased c-Fos expression in both VP and OT neurons by ∼70% and attenuated plasma VP and OT levels by 33% and 35%, respectively. Therefore, NK3R signaling in magnocellular neurons has a critical role for the release of VP and OT in response to hypotension.

Tachykinin neurokinin 3 receptor signaling in cholecystokinin-elicited release of oxytocin and vasopressin

2008 ◽  
Vol 294 (5) ◽  
pp. R1760-R1767 ◽  
Author(s):  
Gwendolen E. Haley ◽  
Francis W. Flynn
Keyword(s):  
Intravenous Injection ◽  
Male Rats ◽  
Endocrine Response ◽  
Blood Samples ◽  
Treatment Groups ◽  
Integral Role ◽  
Freely Behaving ◽  
Baseline Levels ◽  
Neurokinin 3 Receptor ◽  
Intraventricular Treatment

Neurokinin 3 receptor (NK3R) signaling has an integral role in the stimulated oxytocin (OT) and vasopressin (VP) release in response to hyperosmolarity and hypotension. Peripheral injections of cholecystokinin (CCK) receptor agonists for the CCK-A (sulfated CCK-8) and CCK-B (nonsulfated CCK-8) receptors elicit an OT release in rat. It is unknown whether NK3R contributes to this endocrine response. Freely behaving male rats were administered an intraventricular pretreatment of 250 or 500 pmol of SB-222200, a specific NK3R antagonist, or 0.15 M NaCl before an intraperitoneal or intravenous injection of CCK-8 (nonsulfated or sulfated) or 0.15 M NaCl. Blood samples were taken before intraventricular treatment and 15 min after intraperitoneal or intravenous injection, and plasma samples were assayed for OT and VP concentration. Intraperitoneal injection of both nonsulfated and sulfated CCK-8 significantly increased plasma OT levels and had no effect on plasma VP levels. Intravenous injection of sulfated CCK-8 stimulated an increase in plasma OT levels and did not alter plasma VP levels. However, intravenous injection of nonsulfated CCK-8 stimulated a significant increase in plasma levels of both OT and VP. No other studies have demonstrated CCK-8-stimulated release of VP in rat. NK3R antagonist did not alter baseline levels of either hormone. However, pretreatment of NK3R antagonist significantly blocked the CCK-stimulated release of OT in all CCK treatment groups and blocked VP release in response to intravenous injection of nonsulfated CCK-8. Therefore, central NK3R signaling is required for OT and VP release in response to CCK administration.

scholarly journals Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Wanhui Sheng ◽  
Scott W Harden ◽  
Yalun Tan ◽  
Eric G Krause ◽  
Charles J Frazier
Keyword(s):  
Ion Channels ◽  
Paraventricular Nucleus ◽  
Calcium Influx ◽  
Optical Recording ◽  
Magnocellular Neurons ◽  
Axon Terminals ◽  
Dendritic Membrane ◽  
Oxytocin Release ◽  
The Relationship ◽  
Existing Data

Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes, however activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.

Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension

1999 ◽  
Vol 277 (2) ◽  
pp. R532-R540 ◽  
Author(s):  
Kathleen S. Curtis ◽  
J. Thomas Cunningham ◽  
Cheryl M. Heesch
Keyword(s):  
Area Postrema ◽  
Virgin Female ◽  
Female Rats ◽  
Ventrolateral Medulla ◽  
Pregnant Rats ◽  
Induced Hypotension ◽  
Central Response ◽  
Vehicle Treatment ◽  
Fos Expression ◽  
The Brain

Fos and dopamine β-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 ± 2.5 mmHg) than in virgin female rats (121 ± 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

ANG II-induced excitation of paraventricular nucleus magnocellular neurons: a role for glutamate interneurons

2004 ◽  
Vol 286 (5) ◽  
pp. R894-R902 ◽  
Author(s):  
K. J. Latchford ◽  
A. V. Ferguson
Keyword(s):  
Paraventricular Nucleus ◽  
Kynurenic Acid ◽  
Neuronal Excitability ◽  
Critical Role ◽  
Ang Ii ◽  
Magnocellular Neurons ◽  
Whole Cell Patch Clamp ◽  
Electrolyte Homeostasis ◽  
Hypothalamic Slices

The hypothalamic paraventricular nucleus (PVN) plays a critical role in cardiovascular and neuroendocrine regulation. ANG II (ANG) acts throughout the periphery in the maintenance of fluid-electrolyte homeostasis and has also been demonstrated to act as a neurotransmitter in PVN exerting considerable influence on neuronal excitability in this nucleus. The mechanisms underlying the ANG-mediated excitation of PVN magnocellular neurons have yet to be determined. We have used whole cell patch-clamp techniques in hypothalamic slices to examine the effects of ANG on magnocellular neurons. Application of ANG resulted in a depolarization of magnocellular neurons, a response that was abolished in TTX, suggesting an indirect mechanism of action. Interestingly, ANG also increased the frequency of excitatory postsynaptic potentials/currents in magnocellular neurons, an effect that was abolished after application of the glutamate antagonist kynurenic acid. ANG was without effect on the amplitude of excitatory postsynaptic currents, suggesting a presynaptic action on an excitatory interneuron within PVN. The ANG-induced depolarization was shown to be sensitive to kynurenic acid, revealing the requisite role of glutamate in mediating the ANG-induced excitation of magnocellular neurons. These observations indicate that the ANGergic excitation of magnocellular PVN neurons are dependent on an increase in glutamatergic input and thus highlight the importance of a glutamate interneuron in mediating the effects of this neurotransmitter.

scholarly journals The metabolism of four sulphonamides in cows

1973 ◽  
Vol 136 (4) ◽  
pp. 1039-1045 ◽  
Author(s):  
Poul Nielsen
Keyword(s):  
Intravenous Injection ◽  
Acetyl Derivative ◽  
Urine Samples ◽  
Unchanged Drug ◽  
Blood Samples ◽  
Drugs In Blood ◽  
Conjugated Metabolites

1. The metabolism of sulphanilamide, sulphadimidine (4,6-dimethyl-2-sulphanilamidopyrimidine), sulphamethoxazole (5-methyl-3-sulphanilamidoisoxazole) and sulphadoxine (5,6-dimethoxy-4-sulphanilamidopyrimidine) given by intravenous injection has been examined in cows. 2. The sulphonamides were present mainly as unchanged drugs in blood samples collected 2h after administration. 3. The sulphonamides were excreted in the milk partly as unchanged drugs and partly as conjugated metabolites whereas only small amounts were excreted as the N4-acetyl derivatives. 4. The unchanged drug and the N4-acetyl derivative were the major constituents in urine samples after administration of sulphanilamide, sulphamethoxazole and sulphadoxine. 5. Besides the unchanged drug, the N4-acetyl derivative and the conjugated metabolites, three further metabolites of sulphadimidine were isolated from urine samples and identified. They were 5-hydroxy-4,6-dimethyl-2-sulphanilamidopyrimidine, 4-hydroxymethyl-6-methyl-2-sulphanilamidopyrimidine and sulphaguanidine.

219 FOLLICLE AND HORMONE DYNAMICS IN SINGLE- v. DOUBLE-OVULATING HEIFERS

2010 ◽  
Vol 22 (1) ◽  
pp. 267
Author(s):  
M. P. Palhao ◽  
M. A. Beg ◽  
M. T. Rodrigues ◽  
R. R. Araújo ◽  
J. H. M. Viana ◽  
...  
Keyword(s):  
Present Experiment ◽  
Group Effect ◽  
Preovulatory Follicle ◽  
Follicle Growth ◽  
Blood Samples ◽  
Lh Surge ◽  
Follicular Wave ◽  
Preovulatory Follicles ◽  
Main Effect ◽  
Plasma Hormone

The present experiment used the Day 4 ablation model for increasing the incidence of double ovulations in heifers. The objective was to compare follicle growth and plasma hormone concentrations associated with single v. double ovulations. Follicles ≥5 mm were ablated at 4 days post-ovulation to induce a prominent FSH surge and a new follicular wave, and 2 injections of PGF2 (12 h apart) were given 2 days later (Day 6) to favor ovulation. Beginning on Day 5, the 3 largest follicles of the induced wave were scanned twice a day until 36 h after the next ovulation. Blood samples were taken at 6-h intervals starting when the largest follicle reached ≥8.0 mm (expected deviation at 8.5 mm; Ginther et al. 1996) and continued until 36 h after the next ovulation. Concentrations of LH and FSH were measured by validated RIA for cattle (LH measured by Ginther et al. 1999; FSH measured by Adams et al. 1992) and concentrations of oestradiol measured by a commercially available RIA kit (Siddiqui et al. 2009). From a total of 31 heifers, 16 (52%) or 15 (48%) developed a single or more than 1 dominant (≥ 10 mm) follicle in the follicular wave after ablation, respectively. For heifers with 2 dominant follicles, the second-largest follicle ovulated in 9 (60%) heifers and the overall double ovulation rate was 29% (9/31). Follicle diameters and plasma hormone concentrations were compared between single ovulators (n = 12) and double ovulators (n = 8). Diameter of the preovulatory follicles did not increase between the LH peak and ovulation in either the single or double ovulations. In double ovulators, the interval from follicle deviation to the peak of the preovulatory LH surge was shorter (1.9 ± 0.2 days v. 2.5 ± 0.2 days; P < 0.02) and the diameter of the largest preovulatory follicle was smaller (12.2 ± 0.5 mm v. 13.3 ± 0.3 mm; P < 0.02) than in single ovulators, respectively. The LH concentrations of the preovulatory surge did not differ between single and double ovulators for 24 h on each side of the peak (main effect of hour only; P < 0.0001). When data were normalized to the LH peak, the peak of the preovulatory FSH and estradiol surges occurred in synchrony with the peak of LH surge for both groups. A group effect (P < 0.0001) for FSH resulted from a lower concentration averaged over hours in double ovulators. Estradiol showed a group by hour interaction (P < 0.008), reflecting greater concentrations in the double ovulators before and at peak. In conclusion, an increased Supported by the Eutheria Foundation, Cross Plains, WI, USA. Submission supported by FAPEMIG.

scholarly journals Formate concentrations in maternal plasma during pregnancy and in cord blood in a cohort of pregnant Canadian women: relations to genetic polymorphisms and plasma metabolites

2019 ◽  
Vol 110 (5) ◽  
pp. 1131-1137 ◽  
Author(s):  
John T Brosnan ◽  
Lesley Plumptre ◽  
Margaret E Brosnan ◽  
Theerawat Pongnopparat ◽  
Shannon P Masih ◽  
...  
Keyword(s):  
Cord Blood ◽  
Early Pregnancy ◽  
Carbon Metabolism ◽  
Critical Role ◽  
Plasma Concentrations ◽  
Maternal Blood ◽  
Plasma Metabolites ◽  
Blood Samples ◽  
One Carbon Metabolism ◽  
Thymidylate Synthesis

ABSTRACT Background One-carbon metabolism, responsible for purine and thymidylate synthesis and transmethylation reactions, plays a critical role in embryonic and fetal development. Formate is a key player in one-carbon metabolism. In contrast to other one-carbon metabolites, it is not linked to tetrahydrofolate, is present in plasma at appreciable concentrations, and may therefore be distributed to different tissues. Objective The study was designed to determine the concentration of formate in cord blood in comparison with maternal blood taken earlier in pregnancy and at delivery and to relate formate concentrations to potential precursors and key fetal genotypes. Methods Formate and amino acids were measured in plasma during early pregnancy (12–16 wk), at delivery (37–42 wk), and in cord blood samples from 215 mothers, of a prospective cohort study. Three fetal genetic variants in one-carbon metabolism were assessed for their association with cord plasma concentrations of formate. Results The formate concentration was ∼60% higher in the cord blood samples than in mothers’ plasma. The maternal formate concentrations did not differ between the early pregnancy samples and those taken at delivery. Plasma concentrations of 4 formate precursors (serine, glycine, tryptophan, and methionine) were increased in cord blood compared with the maternal samples. Cord blood formate was influenced by fetal genotype, being ∼12% higher in infants harboring the MTHFR A1298C (rs1801131) AC or CC genotypes and 10% lower in infants harboring the MTHFD1 G1958A (rs2236225) GA or AA genotypes. Conclusions The increased formate concentrations in cord blood may support the increased activity of one-carbon metabolism in infants. As such, it would support increased rates of purine and thymidylate synthesis and the provision of methionine for methylation reactions.

Effect of suckling during early lactation and changeover to machine milking on plasma oxytocin and cortisol levels and milking characteristics in Holstein cows

1995 ◽  
Vol 62 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Vladimír Tančin ◽  
L'Ubomír Harcek ◽  
Ján Brouček ◽  
Michal Uhrinčať ◽  
Štefan Mihina
Keyword(s):  
Milk Yield ◽  
Flow Rate ◽  
Plasma Concentrations ◽  
The Other ◽  
Early Lactation ◽  
Flow Rates ◽  
Blood Samples ◽  
Machine Milking ◽  
The Third ◽  
Oxytocin Release

SUMMARYPlasma concentrations of oxytocin and cortisol, and milk yield and flow rates, were compared in three primiparous cows and two cows in their second lactation during suckling and subsequent machine milking. After calving, cows suckled their calves for 3–4 weeks and then the experiment was carried out over 4 d. Blood samples were taken prior to, during and after suckling or evening machine milking (EMM) on day 1 of the experiment (the last day of suckling), day 2 (first EMM) and day 4 (third EMM). After weaning and rehousing, cows were machine milked twice daily. During the first EMM, average milk yield and flow rate in the second minute of milking were significantly lower (P < 0·05) than corresponding values for the other 2 d. Plasma oxytocin concentrations were lower during the first than during the third EMM (P < 0·001) and suckling (P < 0·001), and more oxytocin was released during the third EMM than during suckling (P < 0·01). Cortisol concentrations were higher during and after the first EMM than during the third EMM. Thus in cows sucked for several weeks after calving and then separated from their calves and rehoused we found a transient decrease in oxytocin release, milk yield and flow rates during the first machine milking.

Aligned Expression of IFI16 and STING Genes in RRMS Patients’ Blood

2020 ◽  
Vol 20 (6) ◽  
pp. 878-886
Author(s):  
Sobhan Helbi ◽  
Behnam Ravanbakhsh ◽  
Mohammad Karimi ◽  
Wesam Kooti ◽  
Nahid Jivad
Keyword(s):  
Mrna Level ◽  
Critical Role ◽  
Control Group ◽  
Case Group ◽  
Common Disease ◽  
Type I ◽  
Mrna Levels ◽  
Dna Sensing ◽  
Blood Samples ◽  
Significant Difference

Objective: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the central nervous system. The most common disease phenotype is Relapsing-Remitting MS (RRMS). Beta interferons are the first line of RRMS patients’ treatment. Interferon-inducible protein 16 (IFI16) as a DNA sensing molecule and its downstream complex stimulator of interferon genes (STING) play a critical role in the activation of type I interferons. Hence we aimed to evaluate the expression rate of IFI16 and STING in RRMS patients’ blood under a different type of IFNβ treatment. Methods: In the present study, 99 individuals participated. The participants were divided into 4 groups: 28 control subjects, 25 new cases of RRMS patients, 25 RRMS patients treated with IFNβ-1a (B1a), 21 RRMS patients treated with IFNβ-1b (B1b). The EDTA-treated blood samples were taken and transferred at standard conditions to the Cellular and Molecular Research Center of Shahrekord University of Medical Sciences, RNA was extracted and converted into cDNA. To evaluate the expression of IFI16 and STING, the Real-Time PCR method using SYBR Green/ROX qPCR master mix was performed done. The level of genes expression was measured using 2–ΔΔCt method. The obtained data were analyzed using SPSS v22 software. Results: Comparison of the IFI and STING mRNA expression in blood samples in association with gender and age showed no significant differences (p>0.05). Also, the evaluation of IFI16 mRNA level revealed that the IFI16 genes’ expressions were remarkably higher in the new case group compared to the control group, however, STING expression did not show any significant difference. The mRNA levels of IFI16 and STING in IFNβ-treated groups were significantly lower than the new case group (p<0.001). Also, the genes’ expressions in both the IFNβ-treated groups were significantly lower compared to the control group (p<0.001). In the assessment of the correlation of IFI16 and STING expressions with age and sex in different research groups, no statistically significant differences were seen (p>0.05). Conclusion: Perhaps the IFNβ therapy decreases the IFI16 and STING expression in a STINGdependent pathway as a negative feedback mechanism for regulation of the immune system and suppression of pro-inflammatory cytokines production. The important role of DNA sensing molecules and STING-dependent pathway in MS gives a new insight into future treatment based on STING-direct therapies.

A note on the variability of hormone concentrations in twice-weekly blood samples taken from heifer calves during the first 110 days of life

1981 ◽  
Vol 32 (2) ◽  
pp. 215-217 ◽  
Author(s):  
I. C. Hart ◽  
S. V. Morant ◽  
J. H. B. Roy
Keyword(s):  
Growth Hormone ◽  
Plasma Concentrations ◽  
Early Age ◽  
Production Potential ◽  
Blood Samples ◽  
Plasma Hormone

ABSTRACTTo assess the variability of hormone values obtained from calves at an early age, plasma concentrations of prolactin, growth hormone, insulin and thyroxine were measured in blood samples taken twice-weekly from seven heifers maintained under commercial conditions during their first 110 days of life. With the possible exception of thyroxine, there was considerable variation in the concentration of each hormone in each animal throughout the period of sampling, thus indicating that twice-weekly sampling was inadequate for investigating differences in hormonal concentrations between cattle of different production potential. Although there were trends in the pattern of plasma hormone concentrations as the calves progressed from the pre-ruminant to ruminant states, few of the changes during the pre-weaning, weaning and post-weaning periods were consistent between animals.

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