Role of Calcium in Vomiting: Revelations from the Least Shrew Model of Emesis
Many neurotransmitters/drugs have been implicated in the induction of vomiting
including dopamine, acetylcholine, histamine, opiates, serotonin, substance,
prostaglandins and leukotrienes, to name a few.
Chemotherapeutics such as cisplatin induce vomiting via the release of a number of the above-discussed neurotransmitters/mediators in both the Gastrointestinal tract and the brainstem Dorsal Vagal Complex emetic nuclei including the Nucleus Tractus Solitarius, the Dorsal Motor Nucleus of the Vagus and the Area Postrema Calcium (Ca2+) is one of the simplest yet most dynamic
signaling ions poised at the center of a complex network of signal transduction pathways whose
integration controls cellular pathophysiology. At rest, diverse cells have strict and well-regulated mechanisms to maintain low nM cytosolic Ca2+ levels.
However, in response to synaptic activity, cytosolic Ca2+ can be elevated up to 5 µM.
Thus, agonists can increase cytosolic Ca2+ levels via both mobilization of intracellular stores and influx from extracellular fluid.
The NK1 receptor is G-protein coupled and can increase cytoplasmic Ca2+ concentration via extracellular influx.3-5 In addition, the 5-HT3 receptor
is a Ca2+-permeable ligand-gated ion channel.
HT3 receptor can evoke membrane depolarization which consequently increases cytoplasmic Ca2+
levels via extracellular influx through L-type- and 5-HT3 -receptor Ca2+-permeable channels.6-9 Other emetogens such as agonists of dopamine D2 , 10,11 cholinergic M1 , 12,13 histaminergic H1
14,15 and opiate u16,17-receptors, as well as cisplatin,18 prostaglandins,19,20 rotavirus NSP4 protein21,22 and bacterial toxins23,24 have also the potential to induce extracellular Ca2+ influx.
Therefore Ca2+ mobilization can be an important aspect of emesis induction since it
is involved in triggering neurotransmitter release, coupled with receptor activation and excitation-transcription coupling A variety of Ca2+-permeable ion-channels are present in the plasma membrane, which allow extracellular Ca2+ influx into the cell.
Gastro Open J. 2015; 1(5): 119-128. doi: 10.17140/GOJ-1-121
