Article
Medicine, General & Internal
Kinga Borsodi, Helga Balla, Peter Jozsef Molnar, Adam Lenart, Istvan Kenessey, Andras Horvath, Attila Keszthelyi, Miklos Romics, Attila Majoros, Peter Nyirady, Stefan Offermanns, Zoltan Benyo
Summary: Bradykinin induces contractions in murine and human bladders primarily via activation of B-2 receptors. Simultaneous activation of G alpha(q/11)-coupled and G alpha(12/13)-RhoA-ROCK signaling pathways mediates these contractions, and inhibition of ROCK enzyme can reduce them.
FRONTIERS IN MEDICINE
(2022)
Article
Medicine, Research & Experimental
Jingzhen Zhu, Yi Fan, Qudong Lu, Yang Yang, Hui Li, Xin Liu, Hengshuai Zhang, Bishao Sun, Qian Liu, Jiang Zhao, Zhenxing Yang, Longkun Li, Huan Feng, Jie Xu
Summary: The expression and functional levels of TRPC3, a nonselective cation channel, and NCX1, a Na+/Ca2(+) exchanger, are increased in the bladders of rats with partial bladder outlet obstruction-induced detrusor overactivity. The synergistic effects of TRPC3 and NCX1 significantly increase the concentration of Ca-i(2+) in smooth muscle cells, which induces bladder hyperactivity in this animal model of overactive bladder. TRPC3 and NCX1 may be new therapeutic targets for detrusor overactivity.
LABORATORY INVESTIGATION
(2022)
Review
Physiology
Galina Yu Mironova, Nadia Haghbin, Donald G. G. Welsh
Summary: This article discusses the mechanistic foundation of vascular smooth muscle contraction, including membrane potential, opening of L-type calcium channels, and intracellular rise in Ca2+. It also explores the functional coupling and cooperative behavior of neighboring channels, as well as the impact of channel trafficking on cytoskeleton dynamics.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dariia O. Dryn, Mariia I. Melnyk, Donal Melanaphy, Igor V. Kizub, Christopher D. Johnson, Alexander V. Zholos
Summary: This study demonstrates for the first time the biphasic contractile reaction of TRPV4 in rat pulmonary artery, showing relaxation followed by a contraction. The relaxation phase is induced by BKCa activation, while the subsequent contraction is mediated by TRPV4-dependent depolarization and Ca-L activation. Similar changes in membrane potential are observed with the activation of TRPM8 in the rat tail artery.
Article
Cardiac & Cardiovascular Systems
Yen-Lin Chen, Zdravka Daneva, Maniselvan Kuppusamy, Matteo Ottolini, Thomas M. Baker, Eliska Klimentova, Soham A. Shah, Jennifer D. Sokolowski, Min S. Park, Swapnil K. Sonkusare
Summary: This study demonstrates the role of TRPV4(SMC) channels in blood pressure regulation, showing that their activity increases resting blood pressure in normal mice. The study also reveals the opposite effects of α1AR-TRPV4(SMC) signaling and intraluminal pressure-TRPV4(SMC)-BK channel signaling on blood pressure. In hypertension, constrictor α1AR-PKCα-TRPV4 signaling is upregulated, while dilator pressure-TRPV4-BK channel signaling is disrupted, leading to increased vasoconstriction and elevated blood pressure.
Article
Multidisciplinary Sciences
Ken Lee, Sang O. Park, Pil-Cho Choi, Seung-Bum Ryoo, Haeyeong Lee, Lauren E. Peri, Tong Zhou, Robert D. Corrigan, Andrew C. Yanez, Suk B. Moon, Brian A. Perrino, Kenton M. Sanders, Sang Don Koh
Summary: Volume accommodation in the bladder is regulated by interstitial cells, particularly those expressing PDGFR alpha(+). Spinal cord injury can lead to dysfunction in these cells, causing detrusor overactivity. The downregulation of Pdgfra and Kcnn3, as well as decreased PDGFR alpha(+) cell density and sensitivity to apamin, are key factors in the development of DO after SCI.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
R. Dwivedi, B. T. Drumm, C. S. Griffin, S. Dudem, E. Bradley, T. Alkawadri, S. L. Martin, G. P. Sergeant, M. A. Hollywood, K. D. Thornbury
Summary: Malfunctions in airway smooth muscle Ca2+-signalling causes airway hyperresponsiveness in asthma and chronic obstructive pulmonary disease. Intracellular Ca2+ release plays a crucial role in mediating agonist-induced contractions, but the contribution of L-type Ca2+ channels is still uncertain. This study investigated the involvement of sarcoplasmic reticulum Ca2+ store, store-operated Ca2+ entry (SOCE), and L-type Ca2+ channels in carbachol-induced contractions of mouse bronchial rings and intracellular Ca2+ signals of mouse bronchial myocytes. The results suggest that both SOCE and L-type Ca2+ channels contribute to excitatory cholinergic responses in mouse bronchi, with L-type Ca2+ channels being more significant at lower doses of carbachol or when SOCE is blocked.
Article
Pharmacology & Pharmacy
Keisuke Obara, Mizuki Kaneko, Mio Yamashita, Ge Liu, Kento Yoshioka, Yoshio Tanaka
Summary: The study investigated the role of extracellular Ca2+ influx pathways in enhancing the contractile activities of guinea pig detrusor smooth muscle (DSM) induced by platelet-activating factor (PAF). The results showed that the DSM contractile activities enhanced by PAF were completely inhibited by the removal of extracellular Ca2+ and strongly suppressed by inhibitors of voltage-dependent Ca2+ channels (VDCCs). The remaining contractile activities in the presence of verapamil, a VDCC inhibitor, were not inhibited by LOE-908, an inhibitor of receptor-operated Ca2+ channels (ROCCs), but were almost completely inhibited by SKF96365, an inhibitor of store-operated Ca2+ channels (SOCCs) and ROCCs. Therefore, VDCCs and SOCCs are responsible for the PAF-enhanced DSM contractile activities.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Robert A. Sykes, Karla B. Neves, Rheure Alves-Lopes, Ilaria Caputo, Kirsty Fallon, Nigel B. Jamieson, Anna Kamdar, Assya Legrini, Holly Leslie, Alasdair McIntosh, Alex McConnachie, Andrew Morrow, Richard W. McFarlane, Kenneth Mangion, John McAbney, Augusto C. Montezano, Rhian M. Touyz, Colin Wood, Colin Berry
Summary: Post-COVID-19 conditions are associated with systemic vascular dysfunction, characterized by enhanced arterial constriction and reduced vasorelaxation. Histopathology revealed increased collagen abundance and phosphorylated myosin light chain in COVID-19 arteries. Upregulated gene pathways associated with extracellular matrix alteration and viral mRNA replication were also observed. Activation of Rho-kinase may serve as a novel therapeutic target for post-COVID-19 conditions.
EUROPEAN HEART JOURNAL-CARDIOVASCULAR PHARMACOTHERAPY
(2023)
Article
Cell Biology
Tim Gerwinn, Souzan Salemi, Larissa J. Schori, Dafni Planta, Daniel Eberli, Maya Horst
Summary: This study suggests that bladder detrusor smooth muscle microtissues derived from pediatric ESLUTD patients exhibit improved contractile potential and extracellular matrix composition, which may make them suitable as a cell source for autologous bladder tissue engineering.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Haeyeong Lee, Byoung H. Koh, Lauren E. Peri, Holly J. Woodward, Brian A. Perrino, Kenton M. Sanders, Sang Don Koh
Summary: This study found that after CYP treatment, there is a reduction of PDGFR alpha(+) cells and downregulation of SK3 conductance in the bladder, leading to the development of DO.
SCIENTIFIC REPORTS
(2022)
Review
Physiology
Maria Sancho, Barry D. Kyle
Summary: BK channels facilitate K+ ion efflux from various cells and tissues, with modifications altering their properties and function. While a definitive clinical therapy remains elusive, ongoing research is uncovering potential candidate proteins and mechanisms that modulate BK channel activity. Understanding the diverse properties of BK channels in its various forms remains a key focus of research efforts.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Guohui Zhang, Xianjin Xu, Zhiguang Jia, Yanyan Geng, Hongwu Liang, Jingyi Shi, Martina Marras, Carlota Abella, Karl L. Magleby, Jonathan R. Silva, Jianhan Chen, Xiaoqin Zou, Jianmin Cui
Summary: Researchers have discovered a compound, BC5, that interacts with the CTD-VSD interface and specifically modulates the Ca2+ dependent activation mechanism. BC5 can activate the channel in the absence of Ca2+ binding, but Ca2+ binding inhibits BC5 effects. This study reveals the importance of the CTD-VSD interaction in the Ca2+ activation mechanism and provides insights for allosteric agonists to modulate BK channel activation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jian Liu, Yang Lu, Guancong Li, Min Xiao, Guangming Yang, Yang Pan
Summary: The study found that certain alkaloids from lotus seed embryos have inhibitory effects on ROCK1, with neoliensinine being the most potent inhibitor that leads to relaxation of vascular smooth muscle cells (VSMCs).
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Multidisciplinary Sciences
Po-Ming Chow, Sheng-Mou Hsiao, Hann-Chorng Kuo
Summary: This study identified key factors suggesting urodynamic BOO in women with DU-like profiles and found that volume at first sensation, Qmax, PVR, and DO were independent factors for BOO. The best indicators for BOO were PVR and Qmax.
SCIENTIFIC REPORTS
(2021)
Article
Andrology
Gabriela Reolon Passos, Guilherme Ruiz Leonardi, Mariana Goncalves de Oliveira, Erick de Toledo Gomes, Ana Carolina Ghezzi, Edson Antunes, Fernanda Andrade Orsi, Jose Luiz da Costa, Fabiola Zakia Monica
Summary: This study aimed to assess the effects of serum obtained from unvaccinated men with severe COVID-19 on isolated corpus cavernosum (CC) from mice. The results showed that the relaxation responses in CC incubated with COVID-19 serum were significantly reduced compared to the control serum. However, the relaxation induced by a specific activator was unaffected in CC stimulated with the COVID-19 serum. In addition, COVID-19 serum increased the expression of specific genes. These findings suggest that COVID-19 may lead to erectile dysfunction.
Article
Pharmacology & Pharmacy
Jose Britto-Junior, Antonio Tiago Lima, Rafael Campos, Alexandre Asturiano Giao, Gustavo Duarte Mendes, Luiza P. Ferreira-Novaes P. Silva, Adriano Fregonesi, Andre Sampaio Pupo, Edson Antunes, Gilberto De Nucci
Summary: 6-nitrodopamine (6-ND) is a novel endogenous catecholamine that modulates the contractility of rat isolated epididymal vas deferens (RIEVD). It interacts with classical catecholamines and potentiates their contractions in RIEVD. The activation of adrenergic terminals and pre-synaptic adrenoceptors may contribute to the potentiation of dopamine, noradrenaline, and adrenaline-induced contractions by 6-ND.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Biochemical Research Methods
Gilberto Quirino Junior, Jose Britto-Junior, Tainah Babadopulos Magalhaes, Rafael Campos, Kudzai L. Nyamkondiwa, Kameron L. Klugh, Larryn W. Peterson, Angela Corvino, Rosa Sparaco, Francesco Frecentese, Giuseppe Caliendo, Gilberto De Nucci
Summary: This study presents the validation of a sensitive LC-MS/MS method for determining nitrocatecholamines in Krebs-Henseleit solution. The method was used to investigate the basal release of catecholamines from rabbit isolated atria and ventricles.
BIOMEDICAL CHROMATOGRAPHY
(2023)
Article
Medicine, Research & Experimental
Luis Frederico Gerbase de Oliveira, Jose Britto Junior, Antonio Tiago Lima, Manoel Odorico Moraes, Maria Elisabete A. Moraes, Valeria Barbosa de Souza, Andre Almeida Schenka, Fabiola Zakia Monica, Gilberto De Nucci
Summary: The study found that 6-Nitrodopamine (6-ND) can be released from human umbilical cord vessels and cause vascular relaxation by acting as a dopamine D2-receptor antagonist. It was also found that human peripheral vessels obtained from patients who have undergone surgery for leg amputation release 6-ND and it has action in these tissues. The results indicate that 6-nitrodopamine is released from human peripheral artery and vein rings, and selective dopamine D2-receptor antagonists such as 6-ND may have therapeutic potential in the treatment of human peripheral vascular diseases.
Article
Biology
Jose Britto-Junior, Lincoln Rangel Medeiros-Teixeira, Antonio Tiago Lima, Leticia Costa Dassow, Rodrigo alvaro Brandao Lopes-Martins, Rafael Campos, Manoel Odorico Moraes, Maria Elisabete A. Moraes, Edson Antunes, Gilberto De Nucci
Summary: The study found that 6-nitrodopamine is the major catecholamine released from rat isolated ventricles and is 1000 times more potent than dopamine and noradrenaline in increasing heart inotropism. It is selectively blocked by atenolol.
Article
Biology
J. Britto-Junior, A. T. Lima, J. S. Santos-Xavier, P. Gonzalez, F. Z. Monica, R. Campos, V. B. de Souza, A. A. Schenka, E. Antunes, G. De Nucci
Summary: This study investigated the release of 6-nitrodopamine in the thoracic aorta and pulmonary artery rings of marmosets. The results showed that 6-nitrodopamine is the major catecholamine released by marmoset vascular tissues. It acts as a potent and selective antagonist of dopamine D2-like receptors and induces vasodilation by releasing NO.
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
(2023)
Article
Physiology
Akila L. Oliveira, Matheus L. Medeiros, Ana Carolina Ghezzi, Gabriel Alonso dos Santos, Glaucia Coelho Mello, Fabiola Z. Monica, Edson Antunes
Summary: High levels of MGO and AGEs, along with activation of the RAGE pathway, contribute to diabetes-associated bladder dysfunction. Treatment with the AGE breaker ALT-711 can reduce MGO levels and improve bladder function in diabetic mice.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Carlos Sverdloff, Clive Page, Gilberto De Nucci, Dave Singh
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Ms Vivian Fuguhara, Jose Britto-Junior, Rafael Campos, Silvana Chiavegatto, Fernando Cunha, Edson Antunes, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Luis Frederico Gerbase De Oliveira, Antonio Tiago Lima, Jose Britto-Junior, Rafael Campos, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Antonio Lima, Jose Britto-Junior, Vivian Fuguhara, Edson Antunes, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Gustavo Mendes, Renato Mello, Andre Freitas, Rafael Campos, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Jose Britto-Junior, Antonio Tiago Lima, Rafael Campos, Edson Antunes, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Meeting Abstract
Pharmacology & Pharmacy
Rafael Campos, Jose-Britto Junior, Britto Junior, Gilberto Quirino-Santos, Kudzai L. Nyamkondiwa, Kameron L. Klugh, Dra Larryn W. Peterson, Gilberto De Nucci
BRITISH JOURNAL OF PHARMACOLOGY
(2023)