The Role of Classical Transient Receptor Potential Channels in the Regulation of Hypoxic Pulmonary Vasoconstriction

Author(s):  
B. Fuchs ◽  
A. Dietrich ◽  
T. Gudermann ◽  
H. Kalwa ◽  
F. Grimminger ◽  
...  
Physiology ◽  
2021 ◽  
Vol 36 (5) ◽  
pp. 292-306
Author(s):  
Heather A. Drummond

Loss of pressure-induced vasoconstriction increases susceptibility to renal and cerebral vascular injury. Favored paradigms underlying initiation of the response include transient receptor potential channels coupled to G protein-coupled receptors or integrins as transducers. Degenerin channels may also mediate the response. This review addresses the 1) evolutionary role of these molecules in mechanosensing, 2) limitations to identifying mechanosensitive molecules, and 3) paradigm shifting molecular model for a VSMC mechanosensor.


2021 ◽  
Author(s):  
Amarnath Sen

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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