Canadian journal of physiology and pharmacology最新文献

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Formation of a border ischemic zone depends on plasma potassium concentration. 边界缺血区的形成取决于血浆钾浓度。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-05-01 Epub Date: 2023-12-20 DOI: 10.1139/cjpp-2023-0304
Olesya Bernikova, Aleksandra Durkina, Mikhail Gonotkov, Elena Minnebaeva, Natalia Arteyeva, Jan Azarov
{"title":"Formation of a border ischemic zone depends on plasma potassium concentration.","authors":"Olesya Bernikova, Aleksandra Durkina, Mikhail Gonotkov, Elena Minnebaeva, Natalia Arteyeva, Jan Azarov","doi":"10.1139/cjpp-2023-0304","DOIUrl":"10.1139/cjpp-2023-0304","url":null,"abstract":"<p><p>Extracellular potassium concentration might modify electrophysiological properties in the border zone of ischemic myocardium. We evaluated the depolarization and repolarization characteristics across the ischemic-normal border under [K<sup>+</sup>] variation. Sixty-four-lead epicardial mapping was performed in 26 rats ([K<sup>+</sup>] 2.3-6.4 mM) in a model of acute ischemia/reperfusion. The animals with [K<sup>+</sup>] < 4.7 mM (low-normal potassium) had an ischemic zone with ST-segment elevation and activation delay, a border zone with ST-segment elevation and no activation delay, and a normal zone without electrophysiological abnormalities. The animals with [K<sup>+</sup>] >4.7 mM (normal-high potassium) had only the ischemic and normal zones and no transitional area. Activation-repolarization intervals and local conduction velocities were inversely associated with [K<sup>+</sup>] in linear regression analysis with adjustment for the zone of myocardium. The reperfusion extrasystolic burden (ESB) was greater in the low-normal as compared to normal-high potassium animals. Ventricular tachycardia/fibrillation incidence did not differ between the groups. In patch-clamp experiments, hypoxia shortened action potential duration at 5.4 mM but not at 1.3 mM of [K<sup>+</sup>]. IK(ATP) current was lower at 1.3 mM than at 5.4 mM of [K<sup>+</sup>]. We conclude that the border zone formation in low-normal [K<sup>+</sup>] was associated with attenuation of IK(ATP) response to hypoxia and increased reperfusion ESB.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"331-341"},"PeriodicalIF":2.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138828324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Butorphanol inhibits androgen biosynthesis and metabolism in rat immature Leydig cells in vitro. 布托诺啡醇可抑制体外大鼠未成熟髓质细胞中雄性激素的生物合成和代谢。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2024-01-23 DOI: 10.1139/cjpp-2023-0191
Changchang Li, Lei Shi, Ming Su, Xiaoheng Li, Qiqi Zhu, Ren-Shan Ge, Huitao Li
{"title":"Butorphanol inhibits androgen biosynthesis and metabolism in rat immature Leydig cells in vitro.","authors":"Changchang Li, Lei Shi, Ming Su, Xiaoheng Li, Qiqi Zhu, Ren-Shan Ge, Huitao Li","doi":"10.1139/cjpp-2023-0191","DOIUrl":"10.1139/cjpp-2023-0191","url":null,"abstract":"<p><p>Butorphanol is a synthetic opioid analgesic medication that is primarily used for the management of pain. Butorphanol may have an inhibitory effect on androgen biosynthesis and metabolism in rat immature Leydig cells. The objective of this study was to investigate the influence of butorphanol on androgen secretion by rat Leydig cells isolated from the 35-day-old male rats. Rat Leydig cells were cultured with 0.5-50 μM butorphanol for 3 h in vitro<i>.</i> Butorphanol at 5 and 50 μM significantly inhibited androgen secretion in immature Leydig cells. At 50 μM, butorphanol also blocked the effects of luteinizing hormone (LH) and 8bromo-cAMP-stimulated androgen secretion and 22R-hydroxycholesterol- and pregnenolone-mediated androgen production. Further analysis of the results showed that butorphanol downregulated the expression of genes involved in androgen production, including <i>Lhcgr</i> (LH receptor), <i>Cyp11a1</i> (cholesterol side-chain cleavage enzyme), <i>Srd5a1</i> (5α-reductase 1), and <i>Akr1c14</i> (3α-hydroxysteroid dehydrogenase). Additionally, butorphanol directly inhibited HSD3B1 (3β-hydroxysteroid dehydrogenase 1) and SRD5A1 activity. In conclusion, butorphanol may have side effects of inhibiting androgen biosynthesis and metabolism in Leydig cells.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"270-280"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Existence and importance of Na+K+-ATPase in the plasma membrane of boar spermatozoa. Na+K+- atp酶在猪精子质膜中的存在及其重要性。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2023-11-29 DOI: 10.1139/cjpp-2023-0116
Basim J Awda, Ian V Mahoney, Murray Pettitt, Muhammad Imran, George S Katselis, Mary M Buhr
{"title":"Existence and importance of Na<sup>+</sup>K<sup>+</sup>-ATPase in the plasma membrane of boar spermatozoa.","authors":"Basim J Awda, Ian V Mahoney, Murray Pettitt, Muhammad Imran, George S Katselis, Mary M Buhr","doi":"10.1139/cjpp-2023-0116","DOIUrl":"10.1139/cjpp-2023-0116","url":null,"abstract":"<p><p>Sodium-potassium-ATPase (Na<sup>+</sup>K<sup>+</sup>-ATPase), a target to treat congestive heart failure, is the only known receptor for cardiac glycosides implicated in intracellular signaling and additionally functions enzymatically in ion transport. Spermatozoa need transmembrane ion transport and signaling to fertilize, and Na<sup>+</sup>K<sup>+</sup>-ATPase is identified here for the first time in boar spermatozoa. Head plasma membrane (HPM) isolated from boar spermatozoa was confirmed pure by marker enzymes acid and alkaline phosphatase (218 ± 23% and 245 ± 38% enrichment, respectively, versus whole spermatozoa). Western immunoblotting detected α and β subunits (isoforms α1, α3, β1, β2, and β3) in different concentrations in whole spermatozoa and HPM. Immunofluorescence of intact sperm only detected α3 on the post-equatorial exterior membrane; methanol-permeabilized sperm also had α3 post-equatorially and other isoforms on the acrosomal ridge and cap. Mass spectrometry confirmed the presence of all isoforms in HPM. Incubating boar sperm in capacitating media to induce the physiological changes preceding fertilization significantly increased the percentage of capacitated sperm compared to 0 h control (33.0 ± 2.6% vs. 19.2 ± 2.6% capacitated sperm, respectively; <i>p</i> = 0.014) and altered the β2 immunofluorescence pattern. These results demonstrate the presence of Na<sup>+</sup>K<sup>+</sup>-ATPase in boar sperm HPM and that it changes during capacitation.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"254-269"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tribute-Dr. Pawan K. Singal. 致敬--Pawan K. Singal 博士。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2024-02-28 DOI: 10.1139/cjpp-2024-0046
{"title":"Tribute-Dr. Pawan K. Singal.","authors":"","doi":"10.1139/cjpp-2024-0046","DOIUrl":"10.1139/cjpp-2024-0046","url":null,"abstract":"","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"228"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Uncovering the link between diabetes and cardiovascular diseases: insights from adipose-derived stem cells. 揭示糖尿病与心血管疾病之间的联系:脂肪干细胞的启示。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2024-01-10 DOI: 10.1139/cjpp-2023-0282
Megan B Meechem, Anshul S Jadli, Vaibhav B Patel
{"title":"Uncovering the link between diabetes and cardiovascular diseases: insights from adipose-derived stem cells.","authors":"Megan B Meechem, Anshul S Jadli, Vaibhav B Patel","doi":"10.1139/cjpp-2023-0282","DOIUrl":"10.1139/cjpp-2023-0282","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) are the leading causes of morbidity and mortality worldwide. The escalating global occurrence of obesity and diabetes mellitus (DM) has led to a significant upsurge in individuals afflicted with CVDs. As the prevalence of CVDs continues to rise, it is becoming increasingly important to identify the underlying cellular and molecular mechanisms that contribute to their development and progression, which will help discover novel therapeutic avenues. Adipose tissue (AT) is a connective tissue that plays a crucial role in maintaining lipid and glucose homeostasis. However, when AT is exposed to diseased conditions, such as DM, this tissue will alter its phenotype to become dysfunctional. AT is now recognized as a critical contributor to CVDs, especially in patients with DM. AT is comprised of a heterogeneous cellular population, which includes adipose-derived stem cells (ADSCs). ADSCs resident in AT are believed to regulate physiological cardiac function and have potential cardioprotective roles. However, recent studies have also shown that ADSCs from various adipose tissue depots become pro-apoptotic, pro-inflammatory, less angiogenic, and lose their ability to differentiate into various cell lineages upon exposure to diabetic conditions. This review aims to summarize the current understanding of the physiological roles of ADSCs, the impact of DM on ADSC phenotypic changes, and how these alterations may contribute to the pathogenesis of CVDs.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"229-241"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses. 非诺贝特联合光疗治疗新生儿高胆红素血症的疗效和安全性:一项系统综述和荟萃分析。
IF 1.7 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2023-11-27 DOI: 10.1139/cjpp-2023-0213
Mohammed Abdellatif, Ali Ahmed Fouad Abozaid, Prakesh S Shah, Nacir Dhouibi, Thuan Nguyen-Khac, Rafeef Khleif, Mai Ngoc Luu, Dinh Kim Quyen, Anton Mohareb, Gladson Vaghela, Zeeshan Ali Khan, Hoang Nhat Pham, Abdelrahman M Makram, Nguyen Tien Huy
{"title":"Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses.","authors":"Mohammed Abdellatif, Ali Ahmed Fouad Abozaid, Prakesh S Shah, Nacir Dhouibi, Thuan Nguyen-Khac, Rafeef Khleif, Mai Ngoc Luu, Dinh Kim Quyen, Anton Mohareb, Gladson Vaghela, Zeeshan Ali Khan, Hoang Nhat Pham, Abdelrahman M Makram, Nguyen Tien Huy","doi":"10.1139/cjpp-2023-0213","DOIUrl":"10.1139/cjpp-2023-0213","url":null,"abstract":"<p><p>Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"242-253"},"PeriodicalIF":1.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138443900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Picroside Ⅱ attenuates neuropathic pain by regulating inflammation and spinal excitatory synaptic transmission. PicrosideⅡ通过调节炎症和脊髓兴奋性突触传递减轻神经性疼痛。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2023-11-17 DOI: 10.1139/cjpp-2023-0171
Dongxia Duan, Lian Wang, Yueyang Feng, Daiyu Hu, Donghong Cui
{"title":"Picroside Ⅱ attenuates neuropathic pain by regulating inflammation and spinal excitatory synaptic transmission.","authors":"Dongxia Duan, Lian Wang, Yueyang Feng, Daiyu Hu, Donghong Cui","doi":"10.1139/cjpp-2023-0171","DOIUrl":"10.1139/cjpp-2023-0171","url":null,"abstract":"<p><p>Nerve injury induced microglia activation, which released inflammatory mediators and developed neuropathic pain. Picroside Ⅱ (PⅡ) attenuated neuropathic pain by inhibiting the neuroinflammation of the spinal dorsal horn; however, how it engaged in the cross talk between microglia and neurons remained ambiguous. This study aimed to investigate PⅡ in the modulation of spinal synaptic transmission mechanisms on pain hypersensitivity in neuropathic rats. We investigated the analgesia of PⅡ in mechanical and thermal hyperalgesia using the spinal nerve ligation (SNL)-induced neuropathic pain model and formalin-induced tonic pain model, respectively. RNA sequencing and network pharmacology were employed to screen core targets and signaling pathways. Immunofluorescence staining and qPCR were performed to explore the expression level of microglia and inflammatory mediator mRNA. The whole-cell patch-clamp recordings were utilized to record miniature excitatory postsynaptic currents in excitatory synaptic transmission. Our results demonstrated that the analgesic of PⅡ was significant in both pain models, and the underlying mechanism may involve inflammatory signaling pathways. PⅡ reversed the SNL-induced overexpression of microglia and inflammatory factors. Moreover, PⅡ dose dependently inhibited excessive glutamate transmission. Thus, this study suggested that PⅡ attenuated neuropathic pain by inhibiting excitatory glutamate transmission of spinal synapses, induced by an inflammatory response on microglia.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"281-292"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of sclerostin injection on soleus and extensor digitorum longus muscle tissue in male mice. 硬化剂注射对雄性小鼠比目鱼肌和指长伸肌组织的影响。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-04-01 Epub Date: 2023-11-17 DOI: 10.1139/cjpp-2023-0268
Joshua Stoikos, Nigel Kurgan, Steven Kottaras, Val A Fajardo, William Gittings, Panagiota Klentrou
{"title":"Effects of sclerostin injection on soleus and extensor digitorum longus muscle tissue in male mice.","authors":"Joshua Stoikos, Nigel Kurgan, Steven Kottaras, Val A Fajardo, William Gittings, Panagiota Klentrou","doi":"10.1139/cjpp-2023-0268","DOIUrl":"10.1139/cjpp-2023-0268","url":null,"abstract":"<p><p>Sclerostin, a potent inhibitor of the Wnt signaling pathway, plays a critical role in bone homeostasis. Evidence suggests that sclerostin may also be involved in crosstalk between other tissues, including muscle. This pilot study attempted to examine the effects of sclerostin on soleus and extensor digitorum longus (EDL) muscle tissue from male mice that were given continuous recombinant sclerostin injections for 4 weeks. A total of 48 10-week-old male C57BL/6J mice were assigned to be sedentary or perform 1 h treadmill running per day for 4 weeks and administered subcutaneous injections of either saline or recombinant sclerostin 5 days/week. Sclerostin injection led to a reduction in the soleus myosin heavy chain (MHC) I, MHC I/IIA, MHC IIA/X, and MHC IIB cross-sectional area (<i>p</i> < 0.05) with no exercise effects on these reductions. In contrast, there were no effects of sclerostin injections or exercise on the fast-twitch EDL muscle in terms of size, MHC protein, or markers of Wnt signaling. These findings provide preliminary evidence of sclerostin's endocrine role in muscle via decreases in myofiber cross-sectional area, which seems to be independent of fiber type but muscle type-specific. More studies, however, are needed to confirm these preliminary results.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"293-304"},"PeriodicalIF":2.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta. 咪达唑仑、氟马西尼和新型咪唑并苯二氮唑平MP-III-058对离体大鼠主动脉的血管作用。
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-03-01 Epub Date: 2023-11-01 DOI: 10.1139/cjpp-2023-0285
Milica Gajić Bojić, Marco Treven, Kamal P Pandey, V V N Phani Babu Tiruveedhula, Anja Santrač, Đorđe Đukanović, Nataša Vojinović, Ljiljana Amidžić, Ranko Škrbić, Petra Scholze, Margot Ernst, James M Cook, Miroslav M Savić
{"title":"Vascular effects of midazolam, flumazenil, and a novel imidazobenzodiazepine MP-III-058 on isolated rat aorta.","authors":"Milica Gajić Bojić, Marco Treven, Kamal P Pandey, V V N Phani Babu Tiruveedhula, Anja Santrač, Đorđe Đukanović, Nataša Vojinović, Ljiljana Amidžić, Ranko Škrbić, Petra Scholze, Margot Ernst, James M Cook, Miroslav M Savić","doi":"10.1139/cjpp-2023-0285","DOIUrl":"10.1139/cjpp-2023-0285","url":null,"abstract":"<p><p>Hypotensive influences of benzodiazepines and other GABA<sub>A</sub> receptor ligands, recognized in clinical practice, seem to stem from the existence of \"vascular\" GABA<sub>A</sub> receptors in peripheral blood vessels, besides any mechanisms in the central and peripheral nervous systems. We aimed to further elucidate the vasodilatatory effects of ligands acting through GABA<sub>A</sub> receptors. Using immunohistochemistry, the rat aortic smooth muscle layer was found to express GABA<sub>A</sub> γ2 and α1-5 subunit proteins. To confirm the role of \"vascular\" GABA<sub>A</sub> receptors, we investigated the vascular effects of standard benzodiazepines, midazolam, and flumazenil, as well as the novel compound MP-III-058. Using two-electrode voltage clamp electrophysiology and radioligand binding assays, MP-III-058 was found to have modest binding but substantial functional selectivity for α5β3γ2 over other α<i>x</i>β3γ2 GABA<sub>A</sub> receptors. Tissue bath assays revealed comparable vasodilatory effects of MP-III-058 and midazolam, both of which at 100 µmol/L concentrations had efficacy similar to prazosin. Flumazenil exhibited weak vasoactivity per se, but significantly prevented the relaxant effects of midazolam and MP-III-058. These studies indicate the existence of functional GABA<sub>A</sub> receptors in the rat aorta, where ligands exert vasodilatory effects by positive modulation of the benzodiazepine binding site, suggesting the potential for further quest for leads with optimized pharmacokinetic properties as prospective adjuvant vasodilators.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"206-217"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of prenatal dexamethasone exposure on adult C57BL/6J mouse metabolism and oxidative stress. 产前地塞米松暴露对成年 C57BL/6J 小鼠新陈代谢和氧化应激的影响
IF 2.1 4区 医学
Canadian journal of physiology and pharmacology Pub Date : 2024-03-01 Epub Date: 2024-02-08 DOI: 10.1139/cjpp-2023-0254
A S Nemec-Bakk, J Bel, S Niccoli, D R Boreham, T C Tai, S J Lees, N Khaper
{"title":"Effects of prenatal dexamethasone exposure on adult C57BL/6J mouse metabolism and oxidative stress.","authors":"A S Nemec-Bakk, J Bel, S Niccoli, D R Boreham, T C Tai, S J Lees, N Khaper","doi":"10.1139/cjpp-2023-0254","DOIUrl":"10.1139/cjpp-2023-0254","url":null,"abstract":"<p><p>Prenatal glucocorticoid exposure has been shown to alter hypothalamic-pituitary-adrenal axis function resulting in altered fetal development that can persist through adulthood. Fetal exposure to excess dexamethasone, a synthetic glucocorticoid, has been shown to alter adult behaviour and metabolism. This study investigated the effects prenatal dexamethasone exposure had on adult offspring cardiac and liver metabolism and oxidative stress. Pregnant C57BL/6 mice received a dose of 0.4 mg/kg dexamethasone on gestational days 15-17. Once pups were approximately 7 months old, glucose uptake was determined using positron emission tomography and insulin resistance (IR) was determined by homeostatic model assessment (HOMA) IR calculation. Oxidative stress was assessed by measuring 4-hydroxynonenal protein adduct formation and total reactive oxygen species. Female dexamethasone group had significantly increased glucose uptake when insulin stimulated compared to vehicle-treated mice. HOMA IR revealed no evidence of IR in either male or female offspring. There was also no change in oxidative stress markers in either cardiac or liver tissues of male or female offspring. These data suggest that prenatal dexamethasone exposure in male mice does not alter oxidative stress or metabolism. However, prenatal dexamethasone exposure increased glucocorticoids, cardiac glucose uptake, and pAkt signaling in female heart tissues in adult mice, suggesting there are sex differences in prenatal dexamethasone exposure.</p>","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"180-195"},"PeriodicalIF":2.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139701964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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