ABSTRACT
TRPA1 is a cation channel located on the plasma membrane of many types of human and animal cells, including skin sensory neurons and epithelial cells of the intestine, lungs, urinary bladder, etc. TRPA1 is the major chemosensor that also responds to thermal and mechanical stimuli. Substances that activate TRPA1, e.g., allyl isothiocyanates (pungent components of mustard, horseradish, and wasabi), cinnamaldehyde from cinnamon, organosulfur compounds from garlic and onion, tear gas, acrolein and crotonaldehyde from cigarette smoke, etc., cause burning, mechanical and thermal hypersensitivity, cough, eye irritation, sneezing, mucus secretion, and neurogenic inflammation. An increased activity of TRPA1 leads to the emergence of chronic pruritus and allergic dermatitis and is associated with episodic pain syndrome, a hereditary disease characterized by episodes of debilitating pain triggered by stress. TRPA1 is now considered as one of the targets for developing new anti-inflammatory and analgesic drugs. This review summarizes information on the structure, function, and physiological role of this channel, as well as describes known TRPA1 ligands and their significance as therapeutic agents in the treatment of inflammation-associated pain.
Subject(s)
Analgesics/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Neurogenic Inflammation/drug therapy , Pain/drug therapy , TRPA1 Cation Channel/antagonists & inhibitors , Analgesics/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Humans , Ligands , Molecular Structure , Neurogenic Inflammation/metabolism , Pain/metabolism , TRPA1 Cation Channel/chemistry , TRPA1 Cation Channel/metabolismABSTRACT
Intranasal administration of the polypeptide APHC3, an antagonist of the TRPV1 receptor, had acute anxiolytic and antidepressant effects, as well as an ability to modify the microglial response to proinflammatory stress and cytokine profile of the hippocampus. However, the acute antidepressant effect of the polypeptide was not related to the attenuation of neuroiflammation and probably had a different mechanism. The use of intranasal administration of the APHC3 peptide as a therapeutic approach aimed at decreasing depression symptoms needs additional studies in order to find the mechanism of action of this polypeptide in the central nervous system (CNS).
Subject(s)
Cnidarian Venoms/administration & dosage , Depression/drug therapy , Depression/physiopathology , Hippocampus/drug effects , Hippocampus/physiology , Peptides/administration & dosage , TRPV Cation Channels/antagonists & inhibitors , Administration, Intranasal , Analgesics/administration & dosage , Animals , Anti-Inflammatory Agents/administration & dosage , Antidepressive Agents/administration & dosage , Cytokines/metabolism , Depression/diagnosis , Dose-Response Relationship, Drug , Intercellular Signaling Peptides and Proteins , Male , Rats , Rats, Wistar , TRPV Cation Channels/metabolism , Treatment OutcomeABSTRACT
ÐÐ ÐС1-3 peptides, modulators of TRPV1 receptors, have been administered to SD rats to study their influence on the animal hemostatic system, heart rate, and blood pressure. None of ÐÐРС1-3 polypeptides have any effect on the hemostatic system. Both ÐÐ ÐС1 and ÐÐ ÐС2 polypeptides increased significantly the heart rate, but they did not affect blood pressure, which was probably caused by an ability of these polypeptides to modify animal thermoregulation.
Subject(s)
Blood Coagulation/physiology , Blood Pressure/physiology , Heart Rate/physiology , Hemostasis/physiology , Peptides/administration & dosage , Sea Anemones/chemistry , Animals , Blood Coagulation/drug effects , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Heart Rate/drug effects , Hemostasis/drug effects , Male , Peptides/chemistry , Rats , Rats, Sprague-Dawley , Sea Anemones/classification , Treatment OutcomeABSTRACT
This paper presents data on the activity of a new APHC2 polypeptide modulator of TRPV1 receptors, which was isolated from the sea anemone Heteractis crispa. It has been shown that APHC2 has an analgesic activity, does not impair normal motor activity, and does not change body temperature of experimental animals, which has a great practical value for design of potent analgesics of a new generation. Further study of the characteristics of binding of the polypeptide to the TRPV1 receptor may show approaches to the development of other antagonists of this receptor that do not influence the body temperature.
