TRPV1 has been originally cloned as the heat and capsaicin receptor implicated in acute pain signalling, while further research has shifted the focus to its importance in chronic pain caused by inflammation and associated with this TRPV1 sensitization. However, accumulating evidence suggests that, apart from pain signalling, TRPV1 subserves many other unrelated to nociception functions in the nervous system. In the brain, TRPV1 can modulate synaptic transmission via both pre- and postsynaptic mechanisms and there is a functional crosstalk between GABA receptors and TRPV1. Other fundamental processes include TRPV1 role in plasticity, microglia-to-neuron communication, and brain development. Moreover, TRPV1 is widely expressed in the peripheral tissues, including the vasculature, gastrointestinal tract, urinary bladder, epithelial cells, and the cells of the immune system. TRPV1 can be activated by a large array of physical (heat, mechanical stimuli) and chemical factors (e.g., protons, capsaicin, resiniferatoxin, and endogenous ligands, such as endovanilloids). This causes two general cell effects, membrane depolarization and calcium influx, thus triggering depending on the cell-type diverse functional responses ranging from neuronal excitation to secretion and smooth muscle contraction. Here, we review recent research on the diverse TRPV1 functions with focus on the brain, vasculature, and some visceral systems as the basis of our better understanding of TRPV1 role in different human disorders.

Background: Millions of people worldwide are suffering from Alzheimer's disease (AD), and there are only symptomatic treatments available for this disease. Thus, there is a great need to identify drugs capable of arresting or reversing AD. Constituents of the spice turmeric, in particular, curcuminoids, seem to be very promising, as evident from in vitro experiments and tests using animal models of AD. However, most of the clinical trials did not reveal any beneficial effects of curcuminoids in the treatment of AD. These controversies, including conflicting results of clinical trials, are thought to be related to bioavailability of curcuminoids, which is low unless it is enhanced by developing a special formulation. However, there is growing evidence suggesting that other reasons may be of even greater importance, but these avenues are less explored. Objective: Review relevant literature, and analyze potential reasons for the controversial results. Methodology: Recent in vitro and preclinical studies; clinical trials (without a limiting period) were searched in PubMed and Google Scholar. Results: While recent in vitro and preclinical studies confirm the therapeutic potential of curcuminoids in the treatment of AD and cognitive dysfunctions, results of corresponding clinical trials remain rather controversial. Conclusion: The controversial results obtained in the clinical trials may be in part due to particularities of the curcuminoid formulations other than bioavailability. Namely, it seems likely that the various formulations differ in terms of their minor turmeric constituent(s). We hypothesize that these distinctions may be of key importance for efficacy of the particular formulation in clinical trials. A testable approach addressing this hypothesis is suggested.

Although it was shown that transient receptor potential channels are expressed in the intestinal and myometrial smooth muscle cells and can control gastrointestinal motility and regulate uterine contractility the specific role of transient receptor potential vanilloid-type 4 channel in smooth muscle cells contraction remain largely unknown. The purpose of the study was to test the action of transient receptor potential vanilloid-type 4 selective agonist GSK1016790A on smooth muscle cells contraction in rat’s colon with experimental Parkinson`s disease and in the pregnant rat uterus (18-22 days of gestation). Material and methods. The Parkinson’s disease was induced by single unilateral stereotaxic injection of 12 μg 6-OHDA. The percentage of destroyed dopaminergic neurons was evaluated in apomorphine test (0.5 mg/kg, i.p.) at 1 and 2 weeks after surgery. The water content in faeces was evaluated on the 1st day, then at the 3rd week and 7th month of the experiment. The daily volume of water consumption and gastrointestinal transit time were evaluated at the 3rd week and 7th month after surgery. The action of transient receptor potential vanilloid-type 4 agonist GSK1016790A (0.3 mmol) on smooth muscle cells of colon and myometrium strips contraction was estimated by isometric tension recording. Results and discussion. The apomorphine test showed a progressive increase in the number of turns between the 1st and 2nd week after inducing 6-OHDA-PD. The water content in faeces was increased at the 3rd week (P<0.05) vs. 1st day of the experiment. The rats with 6-OHDA-PD drank less water vs. placebo and intact groups. We observed a 17% delayed GI transit time in 6-OHDA-PD rats (P<0.01) vs. intact and 21% vs. sham-lesioned group of rats 3 weeks after the 6-OHDA treatment. 7 months after the surgery GI transit time was increased more than twice in all studied groups. Transient receptor potential vanilloid-type 4 agonist action on smooth muscle cells of 6-OHDA-PD rats was reduced by 21% compared to intact group and by 46% in sham-lesioned group (P<0.05). After the application of GSK1016790A the rat myometrium strips a 28.4% (P<0.05) decrease of the contractile force was recorded. It was accompanied by a 30.7% (P<0.05) decline of the muscle work estimated as the area under the contractile curve. Suppression of the amplitude of uterine contraction was also followed by a 39.7% (P<0.05) decline of the rise time constant of peaks but unchanged peak duration at the half maximal amplitude. Conclusion. We conclude that pharmacological activation of transient receptor potential vanilloid-type 4 ion channels by their selective agonist GSK1016790A decreased the contractile activity of both colon smooth muscle cells in Parkinson’s disease rats’ model and the myometrium in pregnant rats

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Hepatic bile formation under bombesin action (1 µg/100 g body weight, intraportally) was examined in acute experiments on 30 male rats of three age categories: juvenile (body weight 130-175 g), adult (200-250 g) and elder (more than 300 g). Changes in the bile flow rate were recorded and the amount of various bile acids (BA) was detected using thin layer chromatography/densitometry. Bombesin caused the increase of the bile flow rate in juvenile and adult rats without any effect on it in old animals. The concentration of free bile acids increased in juvenile and adult rats and decreased in old animals. This peptide stimulated secretion of taurocholic and glicocholic acids in adult and aged rats but had no effect on the secretion of tauroconjugated dihydroxycholates. Secretion of dihydroxy bile salts conjugated with glycine was more potently enhanced by bombesin in adult rats but in the elder group this parameter dropped below the control. Bombesin had a lower effect on the BA secretion in aged rats but its influence on the juvenile animals was bidirectional. In this group the peptide stimulates free bile salts formation and, without affecting de novo synthesis, inhibits BA conjugation with amino acids in aged group. Bombesin activated classic pathway of BA biosynthesis in juvenile rats and suppressed it in aged animals. The data obtained demonstrate that different effect of bombesin on bile acids content in rats of different age could change biliary lipid-solubilizing capacity under age related damage of the gut with impairment of normal bombesin release.