Endothelin potentiates TRPV1 via ETA receptor-mediated activation of protein kinase C

© 2007 Plant et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Экспериментальные исследования повышения безопасности подсистемы "оператор"

Приводится анализ условий и безопасности труда операторов мобильных машин при выполнении транспортных работ, влияющих на безопасность. Рассмотрена методика экспериментальных исследований условий труда операторов мобильных машин при транспортных работах. Представлены экспериментальные исследования влияния функциональных возможностей человека-оператора на безопасность транспортных работ. Особенностью выполнения транспортных работ является постоянно изменяющиеся условия производственной среды, которые влияют как на физиологические возможности адаптации оператора, так и на транспортное средство, что вызывает рассогласование между элементами системы оператор-машина-среда и приводит к резкому снижению уровня ее безопасности. Как следствие, требуется поэтапное изучение показателей профессиональной квалификации. Обработка статистического материала и экспериментальных данных позволяет установить взаимосвязь первичного коэффициента квалификации с дискретными значениями стажа работы. Анализ зависимостей тренажа показал, что после пятой повторности эффективность последующих циклов тренажа дает меньший прирост показателя квалификации, чем предыдущий. Имея математическую модель процесса тренажирования, полученную в результате проведения бальной экспертной оценки показателя квалификации, можно определить необходимое число повторности цикла тренажирования для человека-оператора.The article presents the analysis of conditions and labour safety of operators of mobile machines in the fulfillment of transportation work affecting safety. The technique of experimental researches of working conditions of operators of mobile machines in transport operations. Experimental research of the interaction between functional capabilities of the human operator and the security of transport operations. Transport operations are always associated with changing environmental conditions. They affect the physiological capabilities of adaptation of the operator and the reliability of the vehicle. This causes a misalignment between elements of the system operator-machine-environment and leads to a sharp decrease of its security level. This requires a phased study of the indicators of professional qualifications. Processing statistical material and experimental data allows to establish the relationship of initial qualification and level of experience. Dependency analysis when working on the simulator showed that after the fifth repetition, the effectiveness of a subsequent cycle gives a smaller increase of the indicator of skills than the previous cycle. Having a mathematical model of the process of working on the simulator received as a result of the ballroom expert assessment of qualifications, it is possible to define necessary number of repetition of the cycle on the simulator for the human operator

Mass-spectrometric identification of a novel angiotensin peptide in human plasma

Objective— Angiotensin peptides play a central role in cardiovascular physiology and pathology. Among these peptides, angiotensin II (Ang II) has been investigated most intensively. However, further angiotensin peptides such as Ang 1-7, Ang III, and Ang IV also contribute to vascular regulation, and may elicit additional, different, or even opposite effects to Ang II. Here, we describe a novel Ang II-related, strong vasoconstrictive substance in plasma from healthy humans and end-stage renal failure patients. Methods and Results— Chromatographic purification and structural analysis by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an angiotensin octapeptide with the sequence Ala-Arg-Val-Tyr-Ile-His-Pro-Phe, which differs from Ang II in Ala1 instead of Asp1. Des[Asp1]-[Ala1]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp1. Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. In the isolated perfused rat kidney, Ang A revealed a smaller vasoconstrictive effect than Ang II, which was not modified in the presence of the AT2 receptor antagonist PD 123319, suggesting a lower intrinsic activity at the AT1 receptor. Ang II and Ang A concentrations in plasma of healthy subjects and end-stage renal failure patients were determined by matrix-assisted laser desorption/ionisation mass-analysis, because conventional enzyme immunoassay for Ang II quantification did not distinguish between Ang II and Ang A. In healthy subjects, Ang A concentrations were less than 20% of the Ang II concentrations, but the ratio Ang A / Ang II was higher in end-stage renal failure patients. Conclusion— Ang A is a novel human strong vasoconstrictive angiotensin-derived peptide, most likely generated by enzymatic transformation through mononuclear leukocyte-derived aspartate decarboxylase. Plasma Ang A concentration is increased in end-stage renal failure. Because of its stronger agonism at the AT2 receptor, Ang A may modulate the harmful effects of Ang II. In this study, a new angiotensin-peptide of human plasma is described, which is characterized as a strong AT2-receptor agonist

Expression of UV-Sensitive Parapinopsin in the Iguana Parietal Eyes and Its Implication in UV-Sensitivity in Vertebrate Pineal-Related Organs

The pineal-related organs of lower vertebrates have the ability to discriminate different wavelengths of light. This wavelength discrimination is achieved through antagonistic light responses to UV or blue and visible light. Previously, we demonstrated that parapinopsin underlies the UV reception in the lamprey pineal organ and identified parapinopsin genes in teleosts and frogs of which the pineal-related organs were reported to discriminate light. In this study, we report the first identification of parapinopsin in the reptile lineage and show its expression in the parietal eye of the green iguana. Spectroscopic analysis revealed that iguana parapinopsin is a UV-sensitive pigment, similar to lamprey parapinopsin. Interestingly, immunohistochemical analyses using antibodies specific to parapinopsin and parietopsin, a parietal eye green-sensitive pigment, revealed that parapinopsin and parietopsin are colocalized in the outer segments of the parietal eye photoreceptor cells in iguanas. These results strongly suggest that parapinopsin underlies the wavelength discrimination involving UV reception in the iguana parietal eye. The current findings support the idea that parapinopsin is a common photopigment underlying the UV-sensitivity in wavelength discrimination of the pineal-related organs found from lampreys to reptiles

Active zone proteins are dynamically associated with synaptic ribbons in rat pinealocytes

Synaptic ribbons (SRs) are prominent organelles that are abundant in the ribbon synapses of sensory neurons where they represent a specialization of the cytomatrix at the active zone (CAZ). SRs occur not only in neurons, but also in neuroendocrine pinealocytes where their function is still obscure. In this study, we report that pinealocyte SRs are associated with CAZ proteins such as Bassoon, Piccolo, CtBP1, Munc13–1, and the motorprotein KIF3A and, therefore, consist of a protein complex that resembles the ribbon complex of retinal and other sensory ribbon synapses. The pinealocyte ribbon complex is biochemically dynamic. Its protein composition changes in favor of Bassoon, Piccolo, and Munc13–1 at night and in favor of KIF3A during the day, whereas CtBP1 is equally present during the night and day. The diurnal dynamics of the ribbon complex persist under constant darkness and decrease after stimulus deprivation of the pineal gland by constant light. Our findings indicate that neuroendocrine pinealocytes possess a protein complex that resembles the CAZ of ribbon synapses in sensory organs and whose dynamics are under circadian regulation

Stimuli of Sensory-Motor Nerves Terminate Arterial Contractile Effects of Endothelin-1 by CGRP and Dissociation of ET-1/ETA-Receptor Complexes

Endothelin-1 (ET-1), a long-acting paracrine mediator, is implicated in cardiovascular diseases but clinical trials with ET-receptor antagonists were not successful in some areas. We tested whether the quasi-irreversible receptor-binding of ET-1 (i) limits reversing effects of the antagonists and (ii) can be selectively dissociated by an endogenous counterbalancing mechanism.-receptor complexes.-receptors by ET-1 (i) occur at an antagonist-insensitive site of the receptor and (ii) are selectively terminated by endogenously released CGRP. Hence, natural stimuli of sensory-motor nerves that stimulate release of endogenous CGRP can be considered for therapy of diseases involving ET-1

Molecular Evolution of the Neuropeptide S Receptor

The neuropeptide S receptor (NPSR) is a recently deorphanized member of the G protein-coupled receptor (GPCR) superfamily and is activated by the neuropeptide S (NPS). NPSR and NPS are widely expressed in central nervous system and are known to have crucial roles in asthma pathogenesis, locomotor activity, wakefulness, anxiety and food intake. The NPS-NPSR system was previously thought to have first evolved in the tetrapods. Here we examine the origin and the molecular evolution of the NPSR using in-silico comparative analyses and document the molecular basis of divergence of the NPSR from its closest vertebrate paralogs. In this study, NPSR-like sequences have been identified in a hemichordate and a cephalochordate, suggesting an earlier emergence of a NPSR-like sequence in the metazoan lineage. Phylogenetic analyses revealed that the NPSR is most closely related to the invertebrate cardioacceleratory peptide receptor (CCAPR) and the group of vasopressin-like receptors. Gene structure features were congruent with the phylogenetic clustering and supported the orthology of NPSR to the invertebrate NPSR-like and CCAPR. A site-specific analysis between the vertebrate NPSR and the well studied paralogous vasopressin-like receptor subtypes revealed several putative amino acid sites that may account for the observed functional divergence between them. The data can facilitate experimental studies aiming at deciphering the common features as well as those related to ligand binding and signal transduction processes specific to the NPSR

Quality control for unfolded proteins at the plasma membrane

A temperature-sensitive chimeric transmembrane protein reveals a mechanism for disposing misfolded proteins that make it to the plasma membrane

Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease