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Alzheimer's Disease: In Vitro and In Vivo Evidence of Activation of the Plasma Bradykinin-Forming Cascade and Implications for Therapy.
Cells
December 2024
Astria Pharmaceuticals, Boston, MA 02210, USA.
The plaques associated with Alzheimer's disease are formed as a result of the aggregation of Aβ peptides, which vary in length from 38 to 43 amino acids. The 1-40 peptide is the most abundant, while the 1-42 peptide appears to be the most destructive to neurons and/or glial cells in a variety of assays. We have demonstrated that aggregated Aβ, a state prior to plaque formation, will activate the plasma bradykinin-forming pathway when tested in vitro.
View Article and Find Full Text PDFActivation of Bradykinin B Receptors in Astrocytes Stimulates the Release of Leukemia Inhibitory Factor for Autocrine and Paracrine Signaling.
Int J Mol Sci
December 2024
Division of Life Science and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Communications between different cell types within a tissue are often critical for the proper functioning of an organ. In the central nervous system, interactions among neurons and glial cells are known to modulate neurotransmission, energy metabolism, extracellular ion homeostasis, and neuroprotection. Here we showed that bradykinin, a proinflammatory neuropeptide, can be detected by astrocytes, resulting in the secretion of cytokines that act on neurons.
View Article and Find Full Text PDFEstradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.
Elife
December 2024
Department of Chemical Physiology and Biochemistry, Oregon Health & Science University, Portland, United States.
Hypothalamic kisspeptin (Kiss1) neurons are vital for pubertal development and reproduction. Arcuate nucleus Kiss1 (Kiss1) neurons are responsible for the pulsatile release of gonadotropin-releasing hormone (GnRH). In females, the behavior of Kiss1 neurons, expressing Kiss1, neurokinin B (NKB), and dynorphin (Dyn), varies throughout the ovarian cycle.
View Article and Find Full Text PDFNeuronal substance P-driven MRGPRX2-dependent mast cell degranulation products differentially promote vascular permeability.
Front Immunol
December 2024
Department of Science of Allergy and Inflammation, Juntendo University Graduate School of Medicine, Tokyo, Japan.
Mas-related G protein-coupled receptor b2 (Mrgprb2) binding to its cationic endogenous and exogenous ligands induces mast cell degranulation and promotes inflammation in mice. However, the physiological roles of its human homologue MRGPRX2 remain unclear. Here we aimed to elucidate the mechanisms by which MRGPRX2 regulates vascular permeability, and generated MRGPRX2 knock-in (MRGPRX2-KI) and Mrgprb2 knockout (Mrgprb2-KO) mice.
View Article and Find Full Text PDFKinin B1- and B2-Receptor Subtypes Contract Isolated Bovine Ciliary Muscle: Their Role in Ocular Lens Function and Intraocular Pressure Reduction.
Pharmaceuticals (Basel)
November 2024
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX 75207, USA.
Bradykinin is an endogenously produced nonapeptide with many physiological and pathological functions that are mediated by two pharmacologically defined receptor subtypes, B1- and B2-receptors. Current studies sought to characterize the functional bradykinin (BK) receptors present in freshly isolated bovine ciliary muscle (BCM) using an organ-bath tissue contraction system. Cumulative longitudinal isometric tension responses of BCM strips (4-5 mm) were recorded before and after the addition of test compounds to BCM strips hooked up to an isometric strain gauge transducer system.
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