Relaxin acts centrally to inhibit oxytocin release during parturition: an effect that is reversed by naloxone

1986 ◽  
Vol 111 (1) ◽  
pp. 99-102 ◽  
Author(s):  
S. A. Jones ◽  
A. J. S. Summerlee
Keyword(s):  
Jugular Vein ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Opioid System ◽  
Opioid Antagonist ◽  
Unoperated Control ◽  
Osmotic Minipumps ◽  
Oxytocin Release ◽  
Naloxone Treatment

ABSTRACT Experiments were carried out to establish whether infusion of relaxin prolongs gestation and labour in the rat by suppressing release of oxytocin, and whether the effects of relaxin on birth could be reversed by the opioid antagonist naloxone. Female rats were implanted with subcutaneous osmotic minipumps for the infusion of purified porcine relaxin into the jugular vein for 84 h from either day 19 or day 20 of gestation. Infusion of relaxin delayed the onset of labour and in those animals which delivered during relaxin infusion, delivery was longer by approximately 45 min. Plasma oxytocin levels 40 min after delivery of the first fetus were 45·25 ± 3·6 pmol/l (mean ± s.d.) in unoperated controls and significantly (P < 0·01) depressed (23·89 ± 3·9) in rats that delivered during infusion of relaxin. Rats that delivered after the infusion of relaxin had finished, gave birth significantly (P < 0·05) faster than controls and plasma oxytocin levels were significantly (P < 0·01) raised (77·87 ±15·9 pmol/l). Naloxone treatment (1 mg/kg; i.m.) given immediately after the delivery of the first fetus reversed the inhibitory effect of relaxin and the interval between successive deliveries was slightly faster than that of controls. Plasma oxytocin levels in relaxin-infused naloxone-treated rats were significantly (P < 0·01) higher than values in unoperated control rats. The results confirm that relaxin suppresses oxytocin release possibly through an opioid system and this may be important in the control of the timing of birth. J. Endocr. (1986) 111, 99–102

Inhibition of oxytocin release and milk let-down in postpartum primiparous cows is not abolished by naloxone

2001 ◽  
Vol 68 (4) ◽  
pp. 559-568 ◽  
Author(s):  
WOLF-DIETER KRAETZL ◽  
VLADIMIR TANCIN ◽  
DIETER SCHAMS
Keyword(s):  
Post Partum ◽  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Milk Ejection ◽  
Brown Swiss ◽  
Machine Milking ◽  
Oxytocin Release ◽  
Naloxone Treatment ◽  
Vaginal Stimulation

About 10% of primiparous cows have no milk ejection during the first milkings after delivery. Therefore, 17 Brown Swiss dairy cows in their first lactation were used to evaluate the extent of disturbed milk let-down and the corresponding oxytocin (OT) plasma values in the 1st 5 days after delivery. The first milking was 9–22 h after parturition and served for classification of the cows to groups with inhibited (INH), bimodal (BIMO) or normal (NOR) milk let-down. The OT plasma levels before the start of manual teat stimulation and machine milking were comparably high during the first milking especially in NOR and BIMO cows. Ten minutes before the second milking (M2), 300 mg of the opioid antagonist naloxone was injected to test whether the disturbance was affected by the action of endogenous opioids on the neurohypophysis. The milk yield was not influenced by the naloxone treatment, and the INH cows had milk ejection only after a vaginal stimulation. Afterwards, the cows were milked twice every day, until the milk let-down and the OT release were unaffected (equal to control milking). Then, at the next milking, the cows were injected with 300 mg morphine 10 min before milking. The central OT release in response to manual teat stimulation and machine milking was completely blocked in all cows, but a vaginal stimulation was able to abolish this block, at least partially, in 16 cows. Thus, morphine produced a milk let-down characteristic as in the INH cows during the first three milkings. For the following milking, the cows were pre-treated with 300 mg naloxone (−15 min) plus 300 mg morphine (−10 min) before milking. The OT release and the milk yields were unaffected when compared with the control milking. This experiment demonstrates that exogenous opioids can affect the central release of OT in a naloxone-reversible manner even very soon after parturition. However, endogenous opioids are probably not the main mediators of disturbed central OT release and alveolar milk ejection in post-partum primiparous cows.

Effects of porcine relaxin on oxytocin release from the neurohypophysis in the anaesthetized lactating rat

1986 ◽  
Vol 109 (3) ◽  
pp. 393-397 ◽  
Author(s):  
K. T. O'Byrne ◽  
L. Eltringham ◽  
G. Clarke ◽  
A. J. S. Summerlee
Keyword(s):  
Opioid Peptides ◽  
Inhibitory Effect ◽  
Opioid Antagonist ◽  
Dependent Manner ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Oxytocin Release ◽  
Relaxin 2

ABSTRACT The effect of relaxin on electrically evoked release of oxytocin from the posterior pituitary was examined by monitoring changes in intramammary pressure in the anaesthetized lactating rat. The amount of oxytocin released by electrical stimulation of the neurohypophysis in vivo was dramatically reduced following i.v. injection of highly purified porcine relaxin (2·5–10 μg/rat). Relaxin inhibited oxytocin release in a dose-dependent manner and the onset of inhibition occurred within 6–10 min and lasted for 10–60 min. No effect on the sensitivity of the mammary gland to exogenous oxytocin was observed after relaxin treatment. During the period of inhibition, i.v. injection of the opioid antagonist naloxone chloride (1 mg/kg) completely and immediately restored electrically evoked oxytocin release. The neurohypophysis is known to contain endogenous opioid peptides, therefore the effect of relaxin on electrically stimulated release of oxytocin from the rat isolated neural lobe in vitro was examined. Relaxin (500–2000 ng/ml) failed to inhibit oxytocin release in vitro. The results suggest that relaxin can inhibit the release of oxytocin from terminals in the neurohypophysis, but by an indirect mechanism. This action appears to be mediated through endogenous opioid peptides whose source is not clear. They are unlikely to be of neurohypophysial origin and may probably come from the adrenal medulla, since acute adrenalectomy negated the inhibitory effect of relaxin on oxytocin release. J. Endocr. (1986) 109, 393–397

Inhibition of oxytocin release during repeated milking in unfamiliar surroundings: the importance of opioids and adrenal cortex sensitivity

2002 ◽  
Vol 69 (1) ◽  
pp. 63-73 ◽  
Author(s):  
JULIANA MAČUHOVÁ ◽  
VLADIMIR TANČIN ◽  
WOLF-DIETER KRAETZL ◽  
HEINRICH H. D. MEYER ◽  
RUPERT M. BRUCKMAIER
Keyword(s):  
Endogenous Opioids ◽  
Opioid Antagonist ◽  
Control Group ◽  
Research Station ◽  
Milk Ejection ◽  
Milk Flow ◽  
Oxytocin Release ◽  
And Control ◽  
Naloxone Treatment ◽  
Vaginal Stimulation

The aim of this study was to test if the opioid antagonist naloxone has a beneficial effect on normalization of oxytocin (OT) release during repeated milking of cows in unfamiliar surroundings. One control milking without naloxone treatment in all cows was performed in the familiar parlour. For four successive evening milkings, cows were transported to, and milked in, the operating theatre of the research station without (control group) or with naloxone administration (1 mg/kg BW) (naloxone group) before milking. After cessation of spontaneous milk flow, but not before 3 min of milking, vaginal stimulation was applied for 2 min. After milk flow ceased again, 10 IU of OT was injected intravenously to remove the remaining milk including residual milk. Milk flow was recorded continuously and blood samples were collected via a jugular vein cannula at 1-min intervals from 1 min before the start of milking until i.v. injection of OT. The inhibition of milk ejection and its normalization during repeated milking in unfamiliar surroundings was not influenced by naloxone treatment. Concentrations of cortisol and β-endorphin during control milking and all relocations were similar in the naloxone and control groups, although their concentrations were higher after relocations than in the control. Therefore, a role of endogenous opioids in the inhibition of milk ejection in unfamiliar surroundings could not be demonstrated. In addition, the effect of exogenous ACTH1–24 (8 IU, i.v.) on the release of cortisol related to the response of cows milked in unfamiliar surroundings was studied. Cows with totally inhibited milk ejection in response to vaginal stimulation during milking after first relocation had numerically, but not significantly lower cortisol levels (8·8±3·4 ng/ml; AUC/min) in response to ACTH than did cows with at least partial milk ejection (38·7±12·9 ng/ml). Thus animals with a higher adrenal response to ACTH seemed to have less severe inhibition of milk ejection.

Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8

1994 ◽  
Vol 267 (6) ◽  
pp. R1626-R1631 ◽  
Author(s):  
I. Neumann ◽  
R. Landgraf ◽  
Y. Takahashi ◽  
Q. J. Pittman ◽  
J. A. Russell
Keyword(s):  
Supraoptic Nucleus ◽  
Jugular Vein ◽  
Female Rats ◽  
Reproductive Behaviors ◽  
Vasopressin Release ◽  
Hypothalamic Nuclei ◽  
Oxytocin Release ◽  
Left And Right ◽  
Complex Regulation ◽  
The Brain

Simultaneous microdialysis in brain and blood was used to monitor the effects of systemic and central cholecystokinin octapeptide (CCK-8) on the release of oxytocin and vasopressin within the hypothalamic supraoptic nucleus (SON) as well as into blood of urethan-anesthetized female rats. Administration of CCK-8 (20 micrograms/kg iv) increased oxytocin contents in 30-min microdialysates sampled simultaneously within the SON (1.8-fold) and blood (2.4-fold, both P < 0.05) compared with prestimulation levels. In another experiment, after bilateral administration of CCK-8 directly into the SON (10 ng/0.5 microliter) via a microdialysis/infusion probe, oxytocin contents in dialysates sampled from the left and right SON were increased 2.3- and 1.7-fold (P < 0.05), respectively. In simultaneously sampled dialysates from the jugular vein, oxytocin content increased 2.3-fold (P < 0.05). In contrast, oxytocin in dialysates sampled outside the hypothalamic nuclei was not altered by systemic or central CCK-8. The direct infusion of CCK-8 into both SON increased the release of vasopressin within the SON 1.7-fold (P < 0.05) but failed to significantly change vasopressin release into blood. The present findings show a coordinated regulation of intranuclear and systemic release of oxytocin in response to systemic and central CCK-8 and provide further evidence for a possible involvement of endogenous oxytocin in the complex regulation of ingestive and reproductive behaviors induced by CCK-8 at the brain level.

scholarly journals Effect of Potassium Channel Modulators on Morphine Withdrawal in Mice

2010 ◽  
Vol 4 ◽  
pp. SART.S6211 ◽  
Author(s):  
Vikas Seth ◽  
Mushtaq Ahmad ◽  
Prerna Upadhyaya ◽  
Monika Sharma ◽  
Vijay Moghe
Keyword(s):  
Potassium Channel ◽  
Withdrawal Syndrome ◽  
Channel Blocker ◽  
Inhibitory Effect ◽  
Morphine Withdrawal ◽  
The Other ◽  
Opioid Antagonist ◽  
Potassium Channel Openers ◽  
Potassium Channel Modulators ◽  
Withdrawal Signs

The present study was conducted to investigate the effect of potassium channel openers and blockers on morphine withdrawal syndrome. Mice were rendered dependent on morphine by subcutaneous injection of morphine; four hours later, withdrawal was induced by using an opioid antagonist, naloxone. Mice were observed for 30 minutes for the withdrawal signs ie, the characteristic jumping, hyperactivity, urination and diarrhea. ATP-dependent potassium (K+ATP) channel modulators were injected intraperitoneally (i.p.) 30 minutes before the naloxone. It was found that a K+ATP channel opener, minoxidil (12.5–50 mg/kg i.p.), suppressed the morphine withdrawal significantly. On the other hand, the K+ATP channel blocker glibenclamide (12.5–50 mg/kg i.p.) caused a significant facilitation of the withdrawal. Glibenclamide was also found to abolish the minoxidil's inhibitory effect on morphine withdrawal. The study concludes that K+ATP channels play an important role in the genesis of morphine withdrawal and K+ATP channel openers could be useful in the management of opioid withdrawal. As morphine opens K+ATP channels in neurons, the channel openers possibly act by mimicking the effects of morphine on neuronal K+ currents.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

scholarly journals Inhibitory effect of SRIH-14 on ACHT cells in neonatal female rats

2007 ◽  
Vol 59 (2) ◽  
pp. 13P-14P ◽  
Author(s):  
Verica Milosevic ◽  
Milica Terzic ◽  
Milica Manojlovic-Stojanoski ◽  
Natasa Nestorovic ◽  
Milka Sekulic ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Female Rats

scholarly journals EXPERIMENTAL APPROVAL OF THE EFFICACY OF THE COMBINED COMPOSITION RECTAL CREAM NEW TEST-SAMPLES IN THE CONDITIONS OF ACUTE COMPLICATED ANAL FISSURE IN RATS

2019 ◽  
Vol 4 ◽  
pp. 42-49
Author(s):  
Ganna Zaychenko ◽  
Marina Stakhorska
Keyword(s):  
Anal Fissure ◽  
Muscle Tone ◽  
Inhibitory Effect ◽  
Pathological Process ◽  
Female Rats ◽  
Important Place ◽  
Modified Model ◽  
Local Bleeding ◽  
Severity Of The Disease

Anal fissure (AF) is one of the most common anorectal problems. The severity of the disease, the chronicity of the pathological process and frequent complications lead to a sharp deterioration in the quality of life of patients. An important place in the treatment of anal fissure is occupied by drugs that affect its key mechanism of pathogenesis, namely, reduce the muscle tone of the internal anal sphincter and have anti-inflammatory, analgesic, and reparative properties. Aim: conducting of screening studies of the effectiveness of new test samples of rectal cream of the combined composition (RCCC) on the model of acute complicated anal fissure in rats and determining the optimal composition of the potential drug. Materials and methods. The research was conducted on the basis of the Central Scientific Research Laboratory of the National Pharmaceutical University (CSRL NUPH) in the spring (April) season of 2015 on the female rats. A study of test specimens of the rectal cream of the combined composition was performed on a modified model of acute anal fissure. The effectiveness of the treatment was evaluated in terms of (0 to 2) severity of edema, hyperaemia, local bleeding, purulent necrotic processes, scapular formation, anatomical defect, and a general indicator of the severity of the pathological process (by the sum of the points for all the criteria that were analyzed). The level of proinflammatory PGE2 in serum was determined by the immune enzyme method. Results. The RCCC sample No. 4 showed the most expressive therapeutic effect among the four samples under study, and had credible benefits to the inhibitory effect on purulent-necrotic processes, as expressed by the differences in the overall rate of the pathological process (6 days: 5.83±0.47 points against 7.00±0.37; 7.83±0.31 under the influence of RCCC No. 2, No. 3, respectively, and for 11 days 5.00±1.03 versus 6.83±1.28 points (p=0.08 ) under the influence of RCCC No. 1). The ability of RCCCs No.1 and No.4 to reduce the level of pro-inflammatory PGE2 in blood serum of rats compared with CP in 1.8 and 2.0 times, respectively, contributed to accelerating epithelization and scar formation. The advantages of RCCC No. 4 on the comparison of the ointment "Proctozan" with the reduction of the period of epithelization of the defect of the mucous membrane of the anal canal for 3 days (for 7 days – RCCC No. 4, for 10 days - ointment "Proctozan"). Conclusions. The rectal cream of the combined composition No. 4 showed the greatest efficacy, had advantages over the comparison ointment "Proctozan", and is promising for the creation on its basis a new drug for the treatment of anal fissures.

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