Last update 01 Nov 2024

VDCCs x M3 receptor

Last update 01 Nov 2024

Basic Info

Related Targets

VDCCsM3 receptor

Drugs associated with VDCCs x M3 receptor

Temiverine Hydrochloride Hydrate

Target

M3 receptor x VDCCs

Mechanism

M3 receptor antagonists [+1]

Active Org.-

Originator Org.

Nippon Shinyaku Co., Ltd.

Active Indication-

Inactive Indication

Urinary Bladder, Overactive

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with VDCCs x M3 receptor

100 Translational Medicine associated with VDCCs x M3 receptor

0 Patents (Medical) associated with VDCCs x M3 receptor

Literatures (Medical) associated with VDCCs x M3 receptor

01 Jun 2023·Investigative ophthalmology & visual science

High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.

Article

Author: Yin, Yuan ; Niu, Lingzhi ; Wu, Shuai ; Huang, Shiwei

PurposeProliferative diabetic retinopathy (PDR) is characterized by retinal new vessel formation, pointing to the importance of the antiangiogenic treatment in PDR. Hepatocyte nuclear factor 4A (HNF4A) has been highlighted to inhibit vascular endothelial growth factor (VEGF)-stimulated in vitro angiogenesis. Therefore, this study aims to elucidate the potential antiangiogenic mechanisms of HNF4A in PDR.MethodsPDR-related high-throughput sequencing datasets (GSE94019, GSE102485, and GSE191210) were obtained from the Gene Expression Omnibus (GEO) database, followed by the screening of differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the candidate DEGs was constructed based on gene set enrichment analysis (GSEA) data and Search Tool for the Retrieval of Interacting Genes (STRING) data. In addition, the key genes and pathways related to angiogenesis were screened by functional enrichment analysis. Furthermore, human retinal microvascular cells were used for further in vitro validation.ResultsFour key genes (CACNA1A, CACNA1E, PDE1B, and CHRM3) related to PDR were identified in the grey module. CACNA1A affected angiogenesis in PDR by regulating vascular endothelial growth factor A (VEGFA) expression. Furthermore, HNF4A participated in angiogenesis in PDR by activating CACNA1A. In vitro experiments further identified that inhibition of HNF4A reduced CACNA1A expression and increased VEGFA expression, thus promoting angiogenesis in PDR.ConclusionsIn conclusion, the obtained findings suggest that antiangiogenic HNF4A activates the CACNA1A/VEGFA axis in PDR. Our work provides new insights into the angiogenic mechanism of PDR and offers potential targets for translational applications.

01 Jan 2023·Veterinary research forum : an international quarterly journal

Effects of aqueous ginger extract on smooth muscle contraction in bovine cecum: in vitro study.

Article

Author: Maham, Masoud ; Aminfar, Hadi ; Dalir-Naghadeh, Bahram

Intestinal hypomotility cause health risks and economic losses and is considered as an important digestive disorder that efforts to find prokinetic drugs can solve this major problem. This study investigated the effects of Zingiber officinale aqueous extract (ZOAE) on caecal smooth muscle contractions in healthy cows. To perform in vitro tests, cecum strips connected to the organ bath. Ginger aqueous extract caused concentration-dependent contraction in caecal smooth muscle with an effective threshold concentration of 6.00 mg L^-1. The strongest contraction was caused at a concentration of 100 mg L^-1 with an average contraction of 141%. To evaluate the possible mechanisms underlying the contractile effect on cecum strips, atropine, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) and verapamil completely inhibited aqueous extract induced smooth muscle contractions, while addition of hexamethonium had no effect on the contraction process. The lack of reduction of contractions caused by the extract in the presence of hexamethonium indicates that presence of acetylcholine-like constituents independent of nicotinic receptors. The inhibitory properties of atropine and 4-DAMP indicate that at least part of the prokinetic effect of the extract is due to stimulating the muscarinic receptors, especially M3 receptors. Also, verapamil inhibitory function proves that the extract acting by L-type calcium channels. The results suggest that the ZOAE has a potential prokinetic effect which may provide a pharmacological base to its medicinal or prophylactic use in caecal motility disorders.

01 Oct 2022·Diabetes

Smooth Muscle Insulin Receptor Deletion Causes Voiding Dysfunction: A Mechanism for Diabetic Bladder Dysfunction

Article

Author: Zeidel, Mark L. ; Wu, Ali ; Chen, Huan ; Yu, Weiqun

Diabetic bladder dysfunction (DBD) is the most common complication in diabetes. Myogenic abnormalities are common in DBD; however, the underlying mechanisms leading to these remain unclear. To understand the importance of smooth muscle insulin receptor (IR)-mediated signaling in the pathogenesis of DBD, we conditionally deleted it to achieve either heterozygous (SMIR+/−) or homozygous (SMIR−/−) deletion in smooth muscle cells. Despite impaired glucose and insulin tolerance seen with SMIR−/− mice, both SMIR+/− and SMIR−/− mice exhibited normal blood glucose and plasma insulin levels. Interestingly, these mice had abnormal voiding phenotypes, that included urinary frequency and small voids, and bladder smooth muscle (BSM) had significantly diminished contraction force. Morphology revealed a dilated bladder with thinner BSM layer, and BSM bundles were disorganized with penetrating interstitial tissue. Deletion of IR elevated FoxO and decreased mTOR protein expression, which further decreased the expression of Chrm3, P2x1, Sm22, and Cav1.2, crucial functional proteins for BSM contraction. Furthermore, we determined the expression of adiponectin in BSM, and deletion of IR in BSM inhibited adiponectin-mediated signaling. In summary, disruption of IR-mediated signaling in BSM caused abnormalities in proliferation and differentiation, leading to diminished BSM contractility and a voiding dysfunction phenotype that recapitulates human DBD.

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