Prostaglandins E2 and F2alpha potentiate contractile effect induced by adenine nucleotides ATP, ADP and AMP in guinea pig myometrium in vitro. Prostaglandins and nucleotides were added to the organ bath in minute concentrations which have been proved ineffective or slightly contractile when both groups of substances were administered separately. The data of the present work, together with our previously published studies (9, 10, 13), where the action of exogenous adenine nucleotides, NAD and adenosine on rabbit's jejunum in vitro has been proved antagonistic to the contractile effect of various prostaglandins, suggest that prostaglandins and adenine nucleotides appear to block selectively or augment each other's action on various organs. The initial hypothesis that there is a regulatory correlation between endogenous prostaglandins and the function of purinergic nerves also is reinforced.
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http://dx.doi.org/10.1016/0090-6980(76)90032-0 | DOI Listing |
Nat Commun
January 2025
College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China.
Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish nicotinamide metabolism homeostasis.
View Article and Find Full Text PDFScience
January 2025
Redox and Metalloprotein Research Group, Max Planck Institute of Biophysics, Frankfurt am Main, Germany.
In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Physiology and Biophysics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298, United States.
The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Single-Molecule and Cell Mechanobiology Laboratory, Daejeon, 34141, South Korea.
Helicase is a nucleic acid motor that catalyses the unwinding of double-stranded (ds) RNA and DNA via ATP hydrolysis. Helicases can act either as a nucleic acid motor that unwinds its ds substrates or as a chaperone that alters the stability of its substrates, but the two activities have not yet been reported to act simultaneously. Here, we used single-molecule techniques to unravel the synergistic coordination of helicase and chaperone activities, and found that the severe acute respiratory syndrome coronavirus helicase (nsp13) is capable of two modes of action: (i) binding of nsp13 in tandem with the fork junction of the substrate mechanically unwinds the substrate by an ATP-driven synchronous power stroke; and (ii) free nsp13, which is not bound to the substrate but complexed with ADP in solution, destabilizes the substrate through collisions between transient binding and unbinding events with unprecedented melting capability.
View Article and Find Full Text PDFMikrobiyol Bul
January 2025
Kocaeli Üniversitesi Tıp Fakültesi, Tıbbi Mikrobiyoloji Anabilim Dalı, Kocaeli.
Son yıllarda pandemi nedeniyle virüslerin tanı ve tedavisine yönelik terapötik yöntemlerin geliştirilmesi ve antivirallerin test edilmesi amacıyla çok sayıda in vitro çalışma yapılmaktadır. Literatürde SARS-CoV-2'nin modellenebilmesi için HCoV-229E'nin kullanımının güvenli ve yeterli olup olmadığını inceleyen çalışmalar sınırlıdır. Bu sebeple bu çalışmada, BSL-2 şartlarında gerçekleştirilebilen HCoV-229E kültürü ve kantitasyon çalışmalarının, BSL-3 şartları gerektiren SARS-CoV-2 deneylerinde bir ön çalışma modeli olup olamayacağının antiviral etkinlik analizleri üzerinden araştırılması amaçlanmıştır.
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