Background: The spleen is a reservoir for circulating blood cells, and can contract to expel them.
Methods: We have investigated the adrenoceptors involved in isometric contractions of rat spleen produced by noradrenaline (NA) and the α-adrenoceptor agonist phenylephrine (Phe).
Results: Contractions to NA were antagonized by both the α-adrenoceptor antagonist prazosin (10 M) and the α-adrenoceptor antagonist yohimbine (10M), and the combination produced further shifts in NA potency. Contractions to Phe were antagonized by prazosin (10 M) which caused a marked parallel shift in the concentration-response curve. High non-selective concentrations of the α-adrenoceptor antagonist BMY7378 (10 M), the α-adrenoceptor antagonist RS100329 ((3 × 10 M), and the putative α-adrenoceptor antagonist cyclazosin (10 M) also produced parallel shifts in the Phe concentration-response curve. BMY7378 at the selective concentration of 3 × 10 M had no effect on responses to Phe, but RS100329 in the selective concentration of 3 × 10 M produced a marked shift in the effects of high concentrations of Phe. Hence, antagonists in concentrations that block both α- and α-adrenoceptors produce approximately parallel shifts in Phe potency.
Conclusions: Contractions of rat spleen to adrenergic agonists involve α- and α-adrenoceptors, with a lesser role for α-adrenoceptors. This confirms the suggestion that smooth muscle contractions commonly involve multiple subtypes.
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http://dx.doi.org/10.1007/s43440-020-00118-x | DOI Listing |
JCO Clin Cancer Inform
January 2025
Emory University School of Medicine, Atlanta, GA.
Purpose: Immune checkpoint inhibitors (ICIs) have demonstrated promise in the treatment of various cancers. Single-drug ICI therapy (immuno-oncology [IO] monotherapy) that targets PD-L1 is the standard of care in patients with advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%. We sought to find out if a machine learning (ML) algorithm can perform better as a predictive biomarker than PD-L1 alone.
View Article and Find Full Text PDFSci Immunol
January 2025
Department of Cell and Developmental Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Mechanistic understanding of the inhibitory immunoreceptor PD-1 is largely based on mouse models, but human and mouse PD-1 share only 59.6% amino acid identity. Here, we found that human PD-1 is more inhibitory than mouse PD-1, owing to stronger interactions with the ligands PD-L1 and PD-L2 and more efficient recruitment of the effector phosphatase Shp2.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) ion channels are members of the cyclic nucleotide-binding family and are crucial for regulating cellular automaticity in many excitable cells. HCN channel activation contributes to pain perception, and propofol, a widely used anesthetic, acts as an analgesic by inhibiting the voltage-dependent activity of HCN channels. However, the molecular determinants of propofol action on HCN channels remain unknown.
View Article and Find Full Text PDFPLoS One
January 2025
Center of Medical and Bio-Allied Health Sciences Research (CMBHSR), Ajman University, Ajman, United Arab Emirates.
Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role in gene expression regulation, where histone deacetylases (HDACs) are key players in epigenetic processes. Inhibiting HDACs has shown promise in modern cancer therapy.
View Article and Find Full Text PDFAm J Case Rep
January 2025
Department of Obstetrics and Gynecology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
BACKGROUND Studies using transgenic mouse models have demonstrated that estrogen is necessary for the development of cervical cancer, particularly in tissues responsive to estrogen. Estrogen also protects cervical cancer cells from apoptosis, suggesting its role in the survival and persistence of cancer cells. CASE REPORT An 84-year-old woman with diabetes mellitus, hypertension, and stage III chronic renal failure was diagnosed with cervical squamous cell carcinoma, FIGO stage IB2.
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