This article provides an overview of the structure and function of substance P signalling system and its involvement in the cardiovascular regulation. Substance P is an undecapeptide originating from TAC1 gen and belonging to the tachykinin family. The biological actions of substance P are mainly mediated through neurokinin receptor 1 since substance P is the ligand with the highest affinity to neurokinin receptor 1. Substance P is widely distributed within the central and peripheral nervous systems as well as in the cardiovascular system. Substance P is involved in the regulation of heart frequency, blood pressure and in the stretching of vessels. Substance P plays an important role in ischemia and reperfusion and cardiovascular response to stress. Additionally, it has been also implicated in angiogenesis, pain transmission and inflammation. The substance P/neurokinin receptor 1 receptor system is involved in the molecular bases of many human pathological processes. Antagonists of neurokinin receptor 1 receptor could provide clinical solutions for a variety of diseases. Neurokinin receptor 1 antagonists are already used in the prevention of chemotherapy induced nausea and vomiting.
- MeSH
- antagonisté neurokininových receptorů typu 1 farmakologie MeSH
- ischemická choroba srdeční patofyziologie MeSH
- ischemie mozku patofyziologie MeSH
- kardiovaskulární fyziologické jevy * MeSH
- lidé MeSH
- mozek fyziologie MeSH
- nemoci srdce patofyziologie MeSH
- receptory neurokininu-1 fyziologie MeSH
- signální transdukce MeSH
- substance P biosyntéza metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Both adrenomedullin and calcitonin gene-related peptide (CGRP) regulate vascular tone in the heart, being cardioprotective in hypoxia. Additionally, adrenomedullin exhibits antiproliferative and antiapoptotic functions in the myocardium, while CGRP exerts positive chronotropic effect. Their actions are mediated through the specific G protein-coupled receptor, CRLR, whose ligand affinity is determined by receptor activity modifying proteins RAMP1-3. CGRP binds to the complex formed by CRLR/RAMP1, whereas CRLR/RAMP2 and CRLR/RAMP3 serve as receptors for adrenomedullin. Here, we quantified expression of this signaling system in the rat heart and supplying sensory ganglia (dorsal root ganglia T1-T4 and vagal nodose ganglia) in streptozotocin-induced diabetes. In the course of diabetes, an increase of CRLR mRNA was noticed in the right ventricle 8 weeks and of RAMP3 mRNA in the left ventricle and right atrium 26 weeks after induction of diabetes. Relative expressions of other tested genes were not significantly altered. In the nodose vagal supplying specific cardiac afferents, but not in dorsal root ganglia which provide cardiac pain fibres, a small upregulation of CGRP expression was detected. In summary, the shifts observed in diabetes may favour a trend of a pronounced adrenomedullin signaling. These observations may provide a new possible therapeutic strategy for diabetic cardiomyopathy.
- MeSH
- adrenomedulin genetika metabolismus MeSH
- experimentální diabetes mellitus genetika patologie MeSH
- krysa rodu rattus MeSH
- messenger RNA genetika metabolismus MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- protein podobný kalcitoninovému receptoru genetika metabolismus MeSH
- regulace genové exprese * MeSH
- senzorická ganglia metabolismus MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- denervace statistika a číselné údaje MeSH
- experimenty na zvířatech statistika a číselné údaje MeSH
- exprese genu genetika MeSH
- krysa rodu rattus MeSH
- messenger RNA genetika MeSH
- neuropeptid Y analýza genetika MeSH
- srdeční síně anatomie a histologie růst a vývoj MeSH
- sympatický nervový systém fyziologie růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- denervace metody využití MeSH
- financování organizované MeSH
- kontrakce myokardu fyziologie genetika MeSH
- krysa rodu rattus MeSH
- messenger RNA analýza genetika MeSH
- peptid spojený s genem pro kalcitonin biosyntéza genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí využití MeSH
- receptory peptidu se vztahem ke genu kalcitoninu genetika MeSH
- regulace genové exprese genetika MeSH
- srdce inervace růst a vývoj MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
