scholarly journals Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 685 ◽  
Author(s):  
Md. Shahidul Islam
Keyword(s):  
Insulin Secretion ◽  
Electrical Activity ◽  
Islets Of Langerhans ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Β Cells ◽  
Transient Receptor ◽  
Insulinoma Cells

Insulin secretion from the β-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human β-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the β-cells, the α-cells, and some insulinoma cell lines.

Does serotonin deficiency lead to anosmia, ageusia and dysfunctional chemesthesis in COVID-19?

2021 ◽  
Author(s):  
Amarnath Sen
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Taste Receptor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Host Cells ◽  
Potential Channels ◽  
Transient Receptor

Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia of COVID-19 patients, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations of some coronavirus patients remains unknown. It is proposed that in coronavirus patients, there is depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from food, is significantly reduced due to the attack of coronavirus which use ACE2 as the receptor for its entry into the host cells. Incidentally, the depletion of tryptophan should lead to deficiency of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency not only explains fast resolved anosmia and ageusia, but also dysfunctional chemesthesis, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for chemesthetic sensations. The female predominance of olfactory and gustatory dysfunctions can also be explained by considering low 5-HT levels in women. In addition, 5-HT deficiency worsens silent hypoxemia and explains why hypoxic pulmonary vasoconstriction is nearly absent in coronavirus patients leading to poor outcome. Hence, clinical trials should be conducted on coronavirus patients to find out how different selective serotonin reuptake inhibitors (SSRIs) and serotonin agonists work out in eliminating or improving the olfactory, gustatory and chemesthetic dysfunctions as well as hypoxemia.

scholarly journals Transient Receptor Potential Channels as an Emerging Target for the Treatment of Parkinson’s Disease: An Insight Into Role of Pharmacological Interventions

2020 ◽  
Vol 8 ◽  
Author(s):  
Bhupesh Vaidya ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Transient Receptor

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.

Transient receptor potential channels and vascular function

2010 ◽  
Vol 119 (1) ◽  
pp. 19-36 ◽  
Author(s):  
Scott Earley ◽  
Joseph E. Brayden
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Receptor Activation ◽  
Transient Receptor Potential Channels ◽  
No Production ◽  
Control Mechanisms ◽  
Potential Channels ◽  
Transient Receptor

TRP (transient receptor potential) channels play important roles in the regulation of normal and pathological cellular function. In the vasculature, TRP channels are present both in ECs (endothelial cells) and vascular SMCs (smooth muscle cells) and contribute to vasomotor control mechanisms in most vascular beds. Vascular TRP channels are activated by various stimuli, such as mechanical perturbation, receptor activation and dietary molecules. Some of the specific roles of these channels in normal and impaired vascular function have emerged in recent years and include participation in vascular signalling processes, such as neurotransmission, hormonal signalling, NO production, myogenic tone and autoregulation of blood flow, thermoregulation, responses to oxidative stress and cellular proliferative activity. Current research is aimed at understanding the interactions of TRP channels with other vascular proteins and signalling mechanisms. These studies should reveal new targets for pharmacological therapy of vascular diseases, such as hypertension, ischaemia and vasospasm, and vascular proliferative states.

scholarly journals Functional expression of purinergic P2 receptors and transient receptor potential channels by the human urothelium

2013 ◽  
Vol 305 (3) ◽  
pp. F396-F406 ◽  
Author(s):  
Saqib Shabir ◽  
William Cross ◽  
Lisa A. Kirkwood ◽  
Joanna F. Pearson ◽  
Peter A. Appleby ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Functional Expression ◽  
P2 Receptors ◽  
Transient Receptor Potential Channels ◽  
Tissue Homeostasis ◽  
Ligand Selectivity ◽  
Intracellular Ca ◽  
Transient Receptor

In addition to its role as a physical barrier, the urothelium is considered to play an active role in mechanosensation. A key mechanism is the release of transient mediators that activate purinergic P2 receptors and transient receptor potential (TRP) channels to effect changes in intracellular Ca2+. Despite the implied importance of these receptors and channels in urothelial tissue homeostasis and dysfunctional bladder disease, little is known about their functional expression by the human urothelium. To evaluate the expression and function of P2X and P2Y receptors and TRP channels, the human ureter and bladder were used to separate urothelial and stromal tissues for RNA isolation and cell culture. RT-PCR using stringently designed primer sets was used to establish which P2 and TRP species were expressed at the transcript level, and selective agonists/antagonists were used to confirm functional expression by monitoring changes in intracellular Ca2+ and in a scratch repair assay. The results confirmed the functional expression of P2Y4 receptors and excluded nonexpressed receptors/channels (P2X1, P2X3, P2X6, P2Y6, P2Y11, TRPV5, and TRPM8), while a dearth of specific agonists confounded the functional validation of expressed P2X2, P2X4, P2Y1, P2Y2, TRPV2, TRPV3, TRPV6 and TRPM7 receptors/channels. Although a conventional response was elicited in control stromal-derived cells, the urothelial cell response to well-characterized TRPV1 and TRPV4 agonists/antagonists revealed unexpected anomalies. In addition, agonists that invoked an increase in intracellular Ca2+ promoted urothelial scratch repair, presumably through the release of ATP. The study raises important questions about the ligand selectivity of receptor/channel targets expressed by the urothelium. These pathways are important in urothelial tissue homeostasis, and this opens the possibility of selective drug targeting.

scholarly journals Does serotonin deficiency lead to anosmia, ageusia and dysfunctional chemesthesis in COVID-19?

2021 ◽  
Author(s):  
Amarnath Sen
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Taste Receptor ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Host Cells ◽  
Potential Channels ◽  
Transient Receptor

Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia of COVID-19 patients, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations of some coronavirus patients remains unknown. It is proposed that in coronavirus patients, there is depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from food, is significantly reduced due to the attack of coronavirus which use ACE2 as the receptor for its entry into the host cells. Incidentally, the depletion of tryptophan should lead to deficiency of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency not only explains fast resolved anosmia and ageusia, but also dysfunctional chemesthesis, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for chemesthetic sensations. The female predominance of olfactory and gustatory dysfunctions can also be explained by considering low 5-HT levels in women. In addition, 5-HT deficiency worsens silent hypoxemia and explains why hypoxic pulmonary vasoconstriction is nearly absent in coronavirus patients leading to poor outcome. Hence, clinical trials should be conducted on coronavirus patients to find out how different selective serotonin reuptake inhibitors (SSRIs) and serotonin agonists work out in eliminating or improving the olfactory, gustatory and chemesthetic dysfunctions as well as hypoxemia.

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