scholarly journals Muscarinic M2 receptor promotes vasopressin synthesis in mice supraoptic nuclei

2018 ◽  
Vol 237 (2) ◽  
pp. 207-216
Author(s):  
Hiroshi Nagano ◽  
Yuki Sobue ◽  
Hayato Matsuyama ◽  
Shoichiro Saito ◽  
Hiroki Sakai ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Knockout Mice ◽  
Receptor Expression ◽  
Muscarinic Agonist ◽  
Wild Type ◽  
Vasopressin Release ◽  
Paraventricular Nuclei ◽  
Vasopressin Secretion ◽  
Vasopressin Synthesis ◽  
Supraoptic Nuclei

Muscarinic acetylcholine receptors have been suggested to be implicated in arginine–vasopressin secretion because intracerebroventricular muscarinic agonist administration induces arginine–vasopressin release into the circulation. Although which subtype is involved in the regulation of arginine–vasopressin secretion is unclear, M2 receptors have been reported to be highly expressed in the hypothalamus. In the present study, M2 receptor-knockout mice were used to elucidate whether M2 receptor regulates arginine–vasopressin synthesis in the paraventricular nuclei and supraoptic nuclei of the hypothalamus. The number of arginine–vasopressin-immunoreactive neurons in M2 receptor-knockout mice was significantly decreased in the supraoptic nuclei, but not in the paraventricular nuclei compared with wild-type mice. Plasma arginine–vasopressin level in M2 receptor-knockout mice was also significantly lower than in the wild-type mice. Urinary volume and frequency as well as water intake in M2 receptor-knockout mice were significantly higher than those in wild-type mice. The V2 vasopressin receptor expression in kidneys of M2 receptor-knockout mice was comparable with that of wild-type mice, and increased urination in M2 receptor-knockout mice was significantly decreased by administration of desmopressin, a specific V2 receptor agonist, suggesting that V2 receptors in the kidneys of M2 receptor-knockout mice are intact. These results suggest that M2 receptors promote arginine–vasopressin synthesis in the supraoptic nuclei and play a role in the regulation and maintenance of body fluid.

scholarly journals Role of fructose and fructokinase in acute dehydration-induced vasopressin gene expression and secretion in mice

2017 ◽  
Vol 117 (2) ◽  
pp. 646-654 ◽  
Author(s):  
Zhilin Song (宋志林) ◽  
Carlos A. Roncal-Jimenez ◽  
Miguel A. Lanaspa-Garcia ◽  
Sarah A. Oppelt ◽  
Masanari Kuwabara ◽  
...  
Keyword(s):  
Uric Acid ◽  
Aldose Reductase ◽  
Knockout Mice ◽  
Supraoptic Nucleus ◽  
Urinary Concentration ◽  
Wild Type ◽  
Water Restriction ◽  
Vasopressin Release ◽  
Vasopressin Secretion ◽  
Reductase Mrna

Fructose stimulates vasopressin in humans and can be generated endogenously by activation of the polyol pathway with hyperosmolarity. We hypothesized that fructose metabolism in the hypothalamus might partly control vasopressin responses after acute dehydration. Wild-type and fructokinase-knockout mice were deprived of water for 24 h. The supraoptic nucleus was evaluated for vasopressin and markers of the aldose reductase-fructokinase pathway. The posterior pituitary vasopressin and serum copeptin levels were examined. Hypothalamic explants were evaluated for vasopressin secretion in response to exogenous fructose. Water restriction increased serum and urine osmolality and serum copeptin in both groups of mice, although the increase in copeptin in wild-type mice was larger than that in fructokinase-knockout mice. Water-restricted, wild-type mice showed an increase in vasopressin and aldose reductase mRNA, sorbitol, fructose and uric acid in the supraoptic nucleus. In contrast, fructokinase-knockout mice showed no change in vasopressin or aldose reductase mRNA, and no changes in sorbitol or uric acid, although fructose levels increased. With water restriction, vasopressin in the pituitary of wild-type mice was significantly less than that of fructokinase-knockout mice, indicating that fructokinase-driven vasopressin secretion overrode synthesis. Fructose increased vasopressin release in hypothalamic explants that was not observed in fructokinase-knockout mice. In situ hybridization documented fructokinase mRNA in the supraoptic nucleus, paraventricular nucleus and suprachiasmatic nucleus. Acute dehydration activates the aldose reductase-fructokinase pathway in the hypothalamus and partly drives the vasopressin response. Exogenous fructose increases vasopressin release in hypothalamic explants dependent on fructokinase. Nevertheless, circulating vasopressin is maintained and urinary concentrating is not impaired. NEW & NOTEWORTHY This study increases our understanding of the mechanisms leading to vasopressin release under conditions of water restriction (acute dehydration). Specifically, these studies suggest that the aldose reductase-fructokinase pathways may be involved in vasopressin synthesis in the hypothalamus and secretion by the pituitary in response to acute dehydration. Nevertheless, mice undergoing water restriction remain capable of maintaining sufficient vasopressin (copeptin) levels to allow normal urinary concentration. Further studies of the aldose reductase-fructokinase system in vasopressin regulation appear indicated.

M3-receptor knockout mice: muscarinic receptor function in atria, stomach fundus, urinary bladder, and trachea

2002 ◽  
Vol 282 (5) ◽  
pp. R1443-R1449 ◽  
Author(s):  
Peter W. Stengel ◽  
Masahisa Yamada ◽  
Jürgen Wess ◽  
Marlene L. Cohen
Keyword(s):  
Smooth Muscle ◽  
Urinary Bladder ◽  
Muscarinic Receptor ◽  
Knockout Mice ◽  
Smooth Muscle Contraction ◽  
Receptor Activation ◽  
Muscarinic Agonist ◽  
Wild Type ◽  
Atrial Rate ◽  
Stomach Fundus

Negative chronotropic and smooth muscle contractile responses to the nonselective muscarinic agonist carbamylcholine were compared in isolated tissues from M3-muscarinic receptor knockout and wild-type mice. Carbamylcholine (10−8–3.0 × 10−5 M) induced a concentration-dependent decrease in atrial rate that was similar in atria from M3-receptor knockout and wild-type mice, indicating that M3 receptors were not involved in muscarinic receptor-mediated atrial rate decreases. In contrast, the M3 receptor was a major muscarinic receptor involved in smooth muscle contraction of stomach fundus, urinary bladder, and trachea, although differences existed in the extent of M3-receptor involvement among the tissues. Contraction to carbamylcholine was virtually abolished in urinary bladder from M3-receptor knockout mice, suggesting that contraction was predominantly due to M3-receptor activation. However, ∼50–60% maximal contraction to carbamylcholine occurred in stomach fundus and trachea from M3-receptor knockout mice, indicating that contraction in these tissues was also due to M2-receptor activation. High concentrations of carbamylcholine relaxed the stomach fundus from M3-receptor knockout mice by M1-receptor activation. Thus M3-receptor knockout mice provided unambiguous evidence that M3 receptors 1) play no role in carbamylcholine-induced atrial rate reduction, 2) are the predominant receptor mediating carbamylcholine-induced urinary bladder contractility, and 3) share contractile responsibility with M2 receptors in mouse stomach fundus and trachea.

Increased central AT1-receptor activation, not systemic vasopressin, sustains hypertension in ANP knockout mice

2000 ◽  
Vol 278 (6) ◽  
pp. R1441-R1445 ◽  
Author(s):  
Uwe Ackermann ◽  
Newsha Azizi
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Receptor Antagonist ◽  
Knockout Mice ◽  
Blood Pressure Measurement ◽  
Receptor Activation ◽  
Wild Type ◽  
Vasopressin Release ◽  
Arterial Blood ◽  
Left Lateral Ventricle

We tested the hypothesis that hypertension in atrial natriuretic peptide (ANP) knockout mice is caused in part by disinhibition of angiotensin II-mediated vasopressin release. Inactin-anesthetized F2 homozygous ANP gene-disrupted mice (−/−) and wild-type (+/+) littermates were surgically prepared for carotid arterial blood pressure measurement (ABP) and background intravenous injection of physiological saline or vasopressin V1-receptor antagonist (Manning compound, 10 ng/g body wt) and subsequent intracerebroventricular (left lateral ventricle) injection of saline (5 μl) or ANP (0.5 μg) or angiotensin II AT1-receptor antagonist losartan (10 μg). Only (−/−) showed significant decrease in ABP after intracerebroventricular ANP or losartan. Both showed significant hypotension after intravenous V1 antagonist, but there was no difference between their responses. We conclude that 1) vasopressin contributes equally to ABP maintenance in ANP-disrupted mice and wild-type controls; 2) permanently elevated ABP in ANP knockouts is associated with increased central nervous angiotensin II AT1-receptor activation; 3) disinhibition of central nervous angiotensin II AT1receptors in ANP-deficient animals does not lead to a significant increase in the importance of vasopressin as a mechanism for blood pressure maintenance.

Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling

2008 ◽  
Vol 294 (2) ◽  
pp. R344-R351 ◽  
Author(s):  
David A. Bechtold ◽  
Timothy M. Brown ◽  
Simon M. Luckman ◽  
Hugh D. Piggins
Keyword(s):  
Knockout Mice ◽  
Wheel Running ◽  
Neuronal Firing ◽  
Receptor Expression ◽  
Wild Type ◽  
Lighting Condition ◽  
Temporal Regulation ◽  
Running Activity ◽  
Wheel Running Activity ◽  
Feeding Rhythms

The circadian pacemaker in the suprachiasmatic nuclei (SCN) controls endogenous near 24-h physiological and behavioral rhythms in metabolism, neuroendocrine function, and locomotor activity. Recently, we showed that vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2 are critical to the intercellular communication between individual SCN neurons, and appropriate synchronization and phasing of these oscillatory cells. Mice defective in VIP signaling manifest grossly impaired circadian rhythms of SCN neuronal firing activity and are typically unable to maintain rhythmic wheel-running behavior in the absence of external time cues. Here we report that daily rhythms of metabolism and feeding behavior are also overtly altered in these animals. Under diurnal conditions (12:12-h light-dark; LD), metabolic and feeding rhythms are advanced in mice lacking either VIP or VPAC2 receptor expression, peaking in the late day, rather than early night, as observed in wild-type mice. When placed in constant light (LL), both VIP-deficient and VPAC2 receptor-knockout mice exhibit dampening of metabolic and feeding rhythms, which deteriorate after a few days. In addition, overall metabolic rate is greatly reduced in VPAC2-knockout mice, when compared with wild-type mice, regardless of lighting condition. The advancement of metabolic and feeding rhythms in these mice under LD suggests that these rhythms are less sensitive to masking by light. These results demonstrate that altering SCN function not only affects neuronal and wheel-running activity rhythms but also dramatically impairs temporal regulation of metabolism and feeding.

Osmoregulation of vasopressin release and gene transcription under acute and chronic hypovolemia in rats

2004 ◽  
Vol 286 (3) ◽  
pp. E337-E346 ◽  
Author(s):  
Noriko Kondo ◽  
Hiroshi Arima ◽  
Ryouichi Banno ◽  
Shinobu Kuwahara ◽  
Ikuko Sato ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Gene Transcription ◽  
Plasma Volume ◽  
Arginine Vasopressin ◽  
Water Deprivation ◽  
Plasma Osmolality ◽  
Rna Expression ◽  
Salt Loading ◽  
Vasopressin Release ◽  
Paraventricular Nuclei

Although acute decreases in plasma volume are known to enhance the osmotically induced arginine vasopressin (AVP) release, it is unclear whether there is also such interaction at the level of gene transcription. It also remains to be established how sustained changes in plasma volume affect the osmoregulation. In this study, we examined how acute and chronic decreases in blood volume affected the osmoregulation of AVP release and gene transcription in rats. Acute hypovolemia was induced by intraperitoneal injection of polyethylene glycol (PEG), and chronic hypovolemia was induced by 3 days of water deprivation (WD) or 12 days of salt loading (SL). Rats were injected with isotonic or hypertonic saline, and plasma AVP levels and AVP heteronuclear (hn)RNA expression in the supraoptic and paraventricular nuclei, an indicator of gene transcription, were examined in relation to plasma osmolality in each group. Plasma AVP levels were correlated with plasma Na levels in all groups. Whereas the regression lines relating plasma AVP to Na were almost identical among control, WD, and SL groups, the thresholds of plasma Na for AVP release were significantly decreased only in the PEG group. AVP hnRNA levels were also correlated with plasma Na levels in control and PEG groups, and the thresholds were significantly decreased in the PEG group. In contrast, there was no significant correlation of AVP hnRNA and plasma Na levels in WD and SL groups. Thus it was demonstrated that acute and chronic reduction in plasma volume affected the osmoregulation of AVP release and gene transcription in different ways.

Release of oxytocin and vasopressin by magnocellular nuclei in vitro: specific facilitatory effect of oxytocin on its own release

1984 ◽  
Vol 102 (1) ◽  
pp. 63-NP ◽  
Author(s):  
F. Moos ◽  
M. J. Freund-Mercier ◽  
Y. Guerné ◽  
J. M. Guerné ◽  
M. E. Stoeckel ◽  
...  
Keyword(s):  
Paraventricular Nucleus ◽  
Supraoptic Nucleus ◽  
Male Rats ◽  
Facilitatory Effect ◽  
Vasopressin Release ◽  
Paraventricular Nuclei ◽  
Magnocellular Nuclei ◽  
Oxytocin Release ◽  
Supraoptic Nuclei

ABSTRACT The release of endogenous oxytocin and vasopressin by rat paraventricular and supraoptic nuclei in vitro during a 10-min period, 30 min after beginning the incubation, was measured radioimmunologically. Mean basal hormone release per 10 min and per pair of nuclei was: 128·4 ± 12·4 (s.e.m.) pg vasopressin (n = 15) and 39·0 ± 3·0 pg oxytocin (n = 66) for supraoptic nuclei from male rats; 273·9 ± 42·6 pg vasopressin (n = 11) and 34·2 ± 3·5 pg oxytocin (n = 15) for supraoptic nuclei from lactating rats; 70·0 ± 8·6 pg vasopressin (n = 52) and 21·8 ± 1·3 pg oxytocin (n = 68) for paraventricular nuclei from male rats; 59·1 ± 8·6 pg vasopressin (n = 10) and 27·0 ± 4·6 pg oxytocin (n = 16) for paraventricular nuclei from lactating rats. In male and lactating rats, both nuclei contained and released more vasopressin than oxytocin. For oxytocin alone, the paraventricular nucleus of male rats contained and released significantly less hormone than the supraoptic nucleus. This difference was not apparent in lactating rats. For vasopressin alone, the paraventricular nucleus contained and released significantly less hormone than the supraoptic nucleus in both male and lactating rats. When the hormone released was calculated as a percentage of the total tissue content the release was about 0·9% for oxytocin from both nuclei in male and lactating rats and also for vasopressin in lactating rats, but was only about 0·5% for vasopressin from both nuclei in male rats. The influence of oxytocin and analogues of oxytocin (including one antagonist) upon the release of oxytocin and vasopressin was studied. Adding oxytocin to the incubation medium (0·4–4 nmol/l solution) induced a dose-dependent rise in oxytocin release from both nuclei of male or lactating rats. A 4 nmol/l solution of isotocin had a similar effect to a 0·4 nmol/l solution of oxytocin, but arginine-vasopressin never affected basal release of oxytocin. In no case was vasopressin release modified. An oxytocin antagonist (1 μmol/l solution) significantly reduced basal oxytocin release and blocked the stimulatory effect normally induced by exogenous oxytocin, as did gallopamil hydrochloride (D600, 10 μmol/l solution), a Ca2+ channel blocker, or incubation in a Ca2+-free medium. These findings are discussed in relation to the literature on the central effects of neurohypophysial peptides. It may be concluded that the regulatory role of endogenous oxytocin in the hypothalamus on the milk-ejection reflex could result from its local release in the extracellular spaces of magnocellular nuclei. J. Endocr. (1984) 102, 63–72

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