• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.173-182
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• 2018

Recent studies have provided several lines of evidence that peripheral administration of oxytocin induces analgesia in human and rodents. However, the exact underlying mechanism of analgesia still remains elusive. In the present study, we aimed to identify which receptor could mediate the analgesic effect of intraperitoneal injection of oxytocin and its cellular mechanisms in thermal pain behavior. We found that oxytocin-induced analgesia could be reversed by $d(CH_2)_5[Tyr(Me)^2,Dab^5]$ AVP, a vasopressin-1a (V1a) receptor antagonist, but not by $desGly-NH_2-d(CH_2)_5[D-Tyr^2,Thr^4]OVT$, an oxytocin receptor antagonist. Single cell RT-PCR analysis revealed that V1a receptor, compared to oxytocin, vasopressin-1b and vasopressin-2 receptors, was more profoundly expressed in dorsal root ganglion (DRG) neurons and the expression of V1a receptor was predominant in transient receptor potential vanilloid 1 (TRPV1)-expressing DRG neurons. Fura-2 based calcium imaging experiments showed that capsaicin-induced calcium transient was significantly inhibited by oxytocin and that such inhibition was reversed by V1a receptor antagonist. Additionally, whole cell patch clamp recording demonstrated that oxytocin significantly increased potassium conductance via V1a receptor in DRG neurons. Taken together, our findings suggest that analgesic effects produced by peripheral administration of oxytocin were attributable to the activation of V1a receptor, resulting in reduction of TRPV1 activity and enhancement of potassium conductance in DRG neurons.

• Proceedings of the Zoological Society Korea Conference
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• 1999.04a
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• pp.80.2-80
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• 1999

No Abstract, See Full Text

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.269-274
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• 2005

Nephrogenic diabetes insipidus(NBI) is characterized by an inability to concentrate urine despite normal or elevated plasma concentrations of the antidiuretic hormone; arginine vasopressin(AVP). Polyuria with hyposthenuria, and polydipsia are the cardinal clinical manifestations of the disease. Ninety percent of congenital nephrogenic diabetes insipidus patients are males with the X-linked recessive form of the disease; the mutation is in the AVP receptor 2 gene(AVPR2), which is located in chromosomal region Xq28. We report a case of NDI who suffered from unexplained fever and failure to thrive, which has been recognized since about ,3 months after birth. His genomic DNA analysis identified a novel AVPR2 gene mutation as W200C. (J Korean Soc Pediatr Nephrol 2005;9:269-274)

• Childhood Kidney Diseases
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• v.28 no.2
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• pp.51-58
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• 2024

Patients with chronic kidney disease (CKD) bear a significant financial burden and face numerous complications and higher mortality rates. The progression of CKD is associated with glomerular injury caused by glomerular hyperfiltration and oxidative stress. Factors such as uncontrolled hypertension, elevated urine protein levels, anemia, and underlying glomerular disease, contribute to CKD progression. In addition to conservative treatment, several medications are available to combat the progression of CKD to end-stage kidney disease. Renin-angiotensin-aldosterone system blockers could slow the progression of CKD by reducing glomerular hyperfiltration, lowering blood pressure, and decreasing inflammation. Mineralocorticoid receptor antagonists inhibit the mineralocorticoid receptor signaling pathway, thereby attenuating inflammation and fibrosis. Sodium-glucose cotransporter 2 inhibitors exhibit protective effects on the kidneys and against cardiovascular events. Tolvaptan, a selective vasopressin V2-receptor antagonist, decelerates the rate of increase in total kidney volume and deterioration of kidney function in patients with rapidly progressive autosomal dominant polycystic kidney disease. The protective effects of AST-120 remain controversial. Due to a lack of evidence regarding the efficacy and safety of these medications in children, it is imperative to weigh the benefits and adverse effects carefully. Further research is essential to establish the efficacy and safety profiles in pediatric populations.

• The Korean Journal of Physiology
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• v.29 no.1
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• pp.91-102
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• 1995

The role of neurohumoral mechanisms in the regulation of cardiovascular functions and the effects of ethanol (EOH) on these mechanisms were examined in hemorrhaged conscious Wistar rats. The rats were bled at a constant rate (2 ml/kg/min) through the femoral artery until mean arterial pressure (MAP) was reduced by 30 mmHg. We studied the responses to hemorrhage 1) under normal conditions (Normal), and after pretreatments with 2) neural blockade (NB), pentolinium, 3) arginine vasopressin V1-receptor antagonist (AVPX) + NB, 4) angiotensin II ATI-receptor antagonist (AngIIX) + NB, 5) combined humoral blockade (HB), and 6) neurohumoral blockade. Intravenous administration of 30% EOH (6.3 ml/kg) attenuated the baroreceptor reflex sensitivity, and enhanced the depressor action of AngIIX. During hemorrhage, NB produced a faster fall ill MAP than Normal both in the saline and EOH groups. However, HB accelerated the rate of fall in MAP only in the EOH group. The recovery from hemorrhagic hypotension was not different between NB and Normal rats, but was attenuated in HB rats in the saline group. Under NB, AngIIX, but not AVPX, retarded the recovery rate compared with NB alone. EOH attenuated the recovery of MAP after hemorrhage in Normal rats, but completely abolished the recovery in HB rats. We conclude that 1) the maintenance of MAP during hemorrhage is mediated almost entirely by the autonomic functions, 2) angiotensin II plays an important role in the recovery from hemorrhagic hypotension, but AVP assumes little importance, 3) AVP release largely depends on the changes in blood volume, whereas renin release depends on the changes in blood pressure rather than blood volume, and 4) EOH increases the dependence of cardiovascular regulation on angiotensin II and impairs the recovery from hemorrhagic hypotension through the attenuation of autonomic functions.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.209-216
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• 1999

Purpose : Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder associated with renal tubule resistance to arginine vasopressin (AVP). The hypothesis that the defect underlying NDI might be a dysfunctional renal AVPR2 has recently been proven by the identification of mutations in the AVPR2 gene in NDT patients. To investigate the association of mutations in th AVPR2 gene with NDI, we analyzed the AVPR2 gene located on the X chromosome. Methods : We have analyzed the AVPR2 gene in a kindred with X-linked NDI. The proband and proband's mother were analyzed by polymerase chain reaction-single strand conformational polymorphism(PCR-SSCP) and DNA sequencing of the AVPR2 gene. We also have used restriction enzyme analysis of genomic PCR product to evaluate the AVPR2 gene. Results : C to T transition at codon 202, predictive of an exchange of tryptophan 202 by cysteine(R202C) in the third extracellular domain was identified. This mutation causes a loss of Hae III site within the gene. Conclusion : We found a R202C missense mutation in the AVPR2 gene causing X-linked NDI, and now direct mutational analysis is available for carrier screening and early diagnosis.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.255-262
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• 2022

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10^-9-10^-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10^-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.