The regulation of adenylate cyclase by muscarinic cholinergic receptors has been studied in rat heart membranes. In the presence of isoproterenol the K0.5 for Mg2+-mediated activation of adenylate cyclase was 0.1 mM; the addition of the muscarinic receptor agonist oxotremorine increased the K0.5 for Mg2+, and activation by Mg2+ no longer followed mass action kinetics for a single site interaction. The extent of oxotremorine-mediated attenuation of adenylate cyclase exhibited a Mg2+ concentration dependence: in short-time assays at 0.25 mM free Mg2+ the attenuation of enzyme activity was 55 percent, whereas at 20mM Mg2+, only 20 percent inhibition was observed. The increase in the apparent K0.5 for Mg2+ in the presence of oxotremorine was less in 20 min assays than in 4 min assays. The effects of oxotremorine on the rates of activation and deactivation of adenylate cyclase also were examined. Oxotremorine increased the rate of deactivation of adenylate cyclase by two-fold. At low free Mg2+ concentrations, oxotremorine also decreased the rate of activation of adenylate cyclase in the presence of either 0.1 uM GTP gamma S or 1 uM GTP. An oxotremorine-mediated decrease in the rate of activation of adenylate cyclase activity was not detectable in the presence of greater than 3 mM Mg2+.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Zengye decoction regulated the expression of aquaporin in colon tissue of rats with constipation through miR-10a-5p targeting Drd2/AC/cAMP axis.
Histol Histopathol
January 2025
Institute of Anorectal Diseases, School of Integrated Traditional Chinese and Western Medicine Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, PR China.
Slow transit constipation (STC) is a colonic motor disorder characterized by a marked delay in the movement of substances through the colon. Traditional Chinese medicine (TCM) is a treasure trove of natural compounds, which is effective in treating constipation with relatively minor side effects. Zengye decoction (ZYD), a classic herbal formula in TCM, is used for moistening the intestines and relieving constipation.
View Article and Find Full Text PDFEffect of a Low-Molecular-Weight Allosteric Agonist of the Thyroid-Stimulating Hormone Receptor on Basal and Thyroliberin-Stimulated Activity of Thyroid System in Diabetic Rats.
Int J Mol Sci
January 2025
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg 194223, Russia.
The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)--1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM).
View Article and Find Full Text PDFNeural Plasticity in Migraine Chronification.
Eur J Neurosci
January 2025
Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, Plock, Poland.
Chronic migraine (CM) is the ultimate and most burdensome form of the transformation from episodic migraine (EM), called chronification. The mechanism behind migraine chronification is poorly known and difficult to explore as CM has the same spectrum of pathogenesis as EM and the EM-CM transition is bidirectional. Central sensitization (CS) is a key phenomenon in migraine: its mechanisms include disturbed neural plasticity, which is the ability of the nervous system to adapt to endo- and exogenous changes.
View Article and Find Full Text PDFProbing the Signal Transduction Mechanism of the Light-Activated Adenylate Cyclase OaPAC Using Unnatural Amino Acid Mutagenesis.
ACS Chem Biol
January 2025
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400, United States.
OaPAC, the photoactivated adenylyl cyclase from , is composed of a blue light using FAD (BLUF) domain fused to an adenylate cyclase (AC) domain. Since both the BLUF and AC domains are part of the same protein, OaPAC is a model for understanding how the ultrafast modulation of the chromophore binding pocket caused by photoexcitation results in the activation of the output domain on the μs-s time scale. In the present work, we use unnatural amino acid mutagenesis to identify specific sites in the protein that are involved in transducing the signal from the FAD binding site to the ATP binding site.
View Article and Find Full Text PDFSignal Transduction Pathway Mediating Carotid Body Dependent Sympathetic Activation and Hypertension by Chronic Intermittent Hypoxia.
Function (Oxf)
January 2025
Institute for Integrative Physiology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. 60637, USA.
Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia (CIH). OSA patients and CIH-treated rodents exhibit overactive sympathetic nervous system and hypertension, mediated through hyperactive carotid body (CB) chemoreflex. Activation of olfactory receptor 78 (Olfr78) by hydrogen sulfide (H2S) is implicated in CB activation and sympathetic nerve responses to CIH, but the downstream signaling pathways remain unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!