Fetal and Neonatal Development of the Exocrine Pancreas
Jean Morisset, Travis E. Solomon in Growth of the Gastrointestinal Tract: Gastrointestinal Hormones and Growth Factors, 2017
Secretagogues such as CCK and carbachol act by first binding to specific receptors on the surface of the acinar cells. After binding, a series of events collectively termed “stimulus-secretion coupling” take place which finally result in secretion of enzymes from the acinar cells by exocytosis. Pancreatic exocrine secretion is stimulated by secretagogues that act primarily through either the adenylate cyclase system (secretin and vasoactive intestinal polypeptide) or the phosphatidylinositol pathway (CCK and cholinergic agents). The binding of cholecystoki-nin and cholinergic agents to their respective receptors results in the release of inositol trisphosphate and 1,2-diacylglycerol. Inositol trisphosphate induces calcium mobilization and activates calmodulin-dependent protein kinases. At the same time, 1,2-diacyglycerol activates and translocates protein kinase C from a cytosolic to a membraneous site. Taken together, protein kinase C activation, calcium mobilization and subsequent activation of calmodulin dependent protein kinase are viewed as important intermediary steps leading to secretion by the exocrine pancreas.32
Receptors for Neuropeptides: Receptor Isolation Studies and Molecular Biology
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
A class of receptors that can be readily expressed and detected at the level of a single oocyte are those receptors coupled in the cells normally expressing them to the phospholipase C pathway. The oocyte is endowed with such a receptor, i.e., the muscarinic acetylcholine receptor (see Figure 1). As in other systems muscarinic agonist binding leads to phospholipase C activation in the oocyte via a G protein. This results in polyphosphoinositide hydrolysis and formation of inositol trisphosphate, which acts as an intracellular second messenger to release calcium from the endoplasmic reticulum into the cytoplasm. Cytosolic calcium opens a calcium-operated chloride channel (see Figure 1), resulting in a strong depolarizing current that can be measured in a single oocyte by electrophysiological means.44–47 Alternatively, calcium mobilization can be assessed by [45Ca2+] efflux measurement in small groups of oocytes.48
Phosphatidylinositol and inositolphosphatide metabolism in hypertrophied rat heart
H. Saito, Y. Yamori, M. Minami, S.H. Parvez in New Advances in SHR Research –, 2020
Inositol 1, 4, 5-trisphosphate kinase activity. The assay for IP3 kinase activity was performed according to published methods (Irvinet al., 1986). Assays were performed at 37°C in a final volume of 200 ml and initiated by the addition of 100 mg of cytosolic protein. The reaction buffer contained 1 mM of [3H]inositol 1,4,5-trisphosphate (a preliminary experiment revealed a Vmax of 2.2 nmol/min/mg cytosolic protein, and a Km of 1 mM), 50 mM Tris-malate pH7.0, 10 mM ATP, 20 mM MgCl2, 5 mM 2, 3-diphosphoglycerate (2, 3-DPG; this concentration of 2, 3-DPG inhibited the dephosphorylation of IP3 and IP4 by 98%), 10 mM Ca2+. Ca2+ concentration in buffer was determined by prebiously reported method (Renard and Poggioli, 1987). Incubation was carried out for 2 min at 37°C. The reaction was terminated by the addition of 0.5 ml of 15% ice-cold trichloroacetic acid (TCA) and 0.1 ml of 5% bovine serum albumin (BSA), after which TCA was removed by four diethylether washes and the mixture neutralized with NH3. Inositol monophosphate, IP2, IP3 and IP4. were separated by elution from AG 1-X 8 columns in formate form (100-200 mesh; Bio-Rad) by a gradient of ammonium formate (0.2-1.2 M) plus 0.1 M formic acid (Downes et al., 1986; Merritt et al., 1986). For a more detailed analysis, including the separation of inositol phosphate isomers, samples were filtered and separated by high performance-liquid chromatography (Whatman Partisil 10 SAX anion-exchange column with a guard column) with a gradient of ammonium formate and phosphate (Batty et al., 1985; Hawkins et al., 1986).
Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Le Yu Naing, Matthew Heckroth, Prateek Mathur, Thomas L Abell
Substance P is a neuropeptide in the tachykinin peptide family that plays a role in various processes throughout the body, including pain perception and inflammation. Substance P’s receptor, neurokinin type 1 (NK-1 R), is a transmembrane bound receptor located on many cell types including GI vagal afferents and CNS areas involved in the vomiting reflex. It is a G-protein linked receptor that acts through both the inositol trisphosphate/diacylglycerol (IP3/DAG) and cAMP second messenger systems, depending on cell type. The binding of Substance P to NK-1 R in the area postrema and nucleus tractus solitarius triggers emesis. Additionally, in the GI tract, enteric motor neurons release both acetylcholine and substance P onto smooth muscle. Recent animal studies suggest that Substance P, via the NK-1 R, also acts as a co-neurotransmitter important for maintaining muscular responsiveness to acetylcholine and regulating gastric motility[34].
The Wnt/β-catenin pathway in breast cancer therapy: a pre-clinical perspective of its targeting for clinical translation
Published in Expert Review of Anticancer Therapy, 2022
Dezaree Raut, Amisha Vora, Lokesh Kumar Bhatt
The non-canonical Wnt signaling pathway, also known as the β-catenin-independent pathway, is divided into the Wnt/Ca2+ pathway and planar cell polarity (PCP) pathway. In the Wnt/Ca2+ pathway, when Wnt binds to the frizzled (Fz) receptor, it causes intracellular binding of Dvl near the Fz receptor (FZD). In addition to Dvl, the Fz receptor also stimulated trimeric G-protein. Simultaneous stimulation of Dvl and D-protein can activate either Phospholipase (PLC) or Cyclic nucleotide phosphodiesterase (PDE). When PLC is activated, it causes activation of Inositol trisphosphate (IP3). IP3 causes an intracellular release of calcium which further causes calcineurin and CaMK11 activation. CaMK11 activates a nuclear factor of activated T-cells, responsible for cell adhesion, migrations, and tissue separation. On the other hand, calcineurin activates certain substances that interfere with the canonical Wnt signaling pathway to regulate dorsal axis formation negatively. If PDE gets activated, it causes inhibition of calcium release from ER. This pathway helps to regulate intracellular calcium levels by controlling the calcium release from the endoplasmic reticulum [16].
Genetic variants of FGFR family associated with height, hypertension, and osteoporosis
Published in Annals of Human Biology, 2023
Hye-Won Cho, Hyun-Seok Jin, Yong-Bin Eom
Additionally, FGFRs were involved in the calcium signalling pathway, which is essential for endothelial control of cardiovascular and osteoclast activity. Calcium signals at myoendothelial projections are a fundamental factor in endothelial control of vascular tone (Wilson et al. 2019). One study demonstrated disruption in calcium signalling mediated by inositol trisphosphate (IP3), which results in release of calcium and creates microdomains that are essential to the balance of vascular function, in hypertensive rats (Yuan et al. 2016; Lin et al. 2019; Wilson et al. 2019). In addition, from the bone homeostasis point of view, it is well-known that calcium is essential for activating proliferation of osteoclast precursors and suppressing the resorption of mature osteoclasts (Kajiya 2012). Calcium homeostasis in bone is monitored by parathyroid hormone (PTH). The parathyroid gland has calcium-sensing membrane receptors, and a low level of calcium releases PTH, followed by stimulation of osteoclasts (Teitelbaum 2000).
Related Knowledge Centers
- Diglyceride
- Hydrolysis
- Phospholipase C
- Phospholipid
- Second Messenger System
- Signal Transduction
- Cell Membrane
- Inositol Phosphate
- Phosphatidylinositol 4,5-Bisphosphate
- Cell