scholarly journals Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Sven Dannhäuser ◽  
Thomas J Lux ◽  
Chun Hu ◽  
Mareike Selcho ◽  
Jeremy T-C Chen ◽  
...  
Keyword(s):  
High Threshold ◽  
Mechanical Stimuli ◽  
In Vivo Experiments ◽  
Physiological Processes ◽  
Signal Discrimination ◽  
Low Threshold ◽  
Sensory Responses ◽  
Opposing Effects ◽  
Adhesion Gpcr

Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the Drosophila aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic in vivo experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased Cirl1 expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.

scholarly journals Antinociceptive modulation by the adhesion-GPCR CIRL promotes mechanosensory signal discrimination

2020 ◽  
Author(s):  
Sven Dannhäuser ◽  
Thomas J. Lux ◽  
Chun Hu ◽  
Mareike Selcho ◽  
Jeremy Tsung-Chieh Chen ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Physiological Processes ◽  
Signal Discrimination ◽  
Low Threshold ◽  
Sensory Responses ◽  
Adhesion Gpcr ◽  
G Protein Coupled

ABSTRACTAdhesion-type G protein-coupled receptors (aGPCRs) participate in a vast range of physiological processes. Correspondingly, these receptors are associated with diverse human diseases, such as developmental disorders, defects of the nervous system, allergies and cancer. Several aGPCRs have recently been linked to mechanosensitive functions suggesting that processing of mechanical stimuli may be a common feature of this receptor family. CIRL (ADGRL/Latrophilin, LPHN), one of the oldest members of the aGPCR family, sensitizes sensory responses of larval Drosophila to gentle touch and sound by amplifying mechanosensory signal transduction in low-threshold mechanoreceptors (Scholz et al., 2015; 2017). In the present study, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathophysiological conditions. Optogenetic in vivo experiments indicate that CIRL quenches cAMP levels in both mechanosensory submodalities. However, contrasting its effect in touch sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display a drop in Cirl1 expression during allodynia. Taken together, these results demonstrate that CIRL exerts opposing modulatory functions in low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action likely facilitates the separation of mechanosensory signals carrying different physiological information.

Food supplement “carrageenan” and its effect on the organism

2020 ◽  
Author(s):  
O.E. Luneva ◽  
Keyword(s):  
Gastrointestinal Tract ◽  
Food Additives ◽  
Food Supplement ◽  
The Body ◽  
Laboratory Rats ◽  
Experimental Part ◽  
In Vivo Experiments ◽  
Physiological Processes

Food additives are positioned as harmless, although, their components affectthe physiological processes associated with the permeability of the wall of the gastrointestinal tract (GIT) and intestinal microbiota. This article describes thecarrageenan supplement and its effects on the body in in vitro and in vivo experiments. The experimental part is devoted to analysis of the intestinalmicrobiota of laboratory rats with the consumption of the carrageenan dietary supplement in the amount of about 4,4 % of the standard feed.

Excitation of primate spinothalamic neurons by cutaneous C-fiber volleys

1979 ◽  
Vol 42 (5) ◽  
pp. 1354-1369 ◽  
Author(s):  
J. M. Chung ◽  
D. R. Kenshalo ◽  
K. D. Gerhart ◽  
W. D. Willis
Keyword(s):  
Dynamic Range ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Spinothalamic Tract ◽  
Noxious Heat ◽  
C Fibers ◽  
C Fiber ◽  
Excitatory Action ◽  
Low Threshold ◽  
Lateral Nucleus

1. The responses of spinothalamic tract cells in the lumbosacral spinal cords of anesthetized monkeys were examined following electrical stimulation of the sural nerve or the application of noxious thermal and mechanical stimuli to the skin on the lateral aspect of the foot. 2. The spinothalamic tract neurons were classified as wide dynamic range (WDR), high-threshold (HT), or low-threshold (LT) cells on the basis of their responses to mechanical stimuli. 3. All of the WDR and HT spinothalamic tract cells tested responded to volleys in A- and C-fibers. However, strong C-fiber responses were more common in HT than in WDR cells. 4. The responses atributed to C-fibers were graded with the size of the C-fiber volley. The latencies of the responses attributed to C-fibers indicated that the fastest afferents involved had a mean conduction velocity of 0.9 m/s. The responses remained after anodal blockade of conduction in A-fibers. 5. Temporal summation of the responses of spinothalamic tract cells was demonstrated both to brief trains of stimuli at 33 Hz and to single stimuli repeated at 1- to 2-s intervals. The latter phenomenon is often called "windup." 6. The responses of several spinothalamic tract cells to noxious heat pulses could still be elicited during anodal blockade of conduction in A-fibers. Similarly, it was possible to demonstrate an excitatory action of noxious mechanical stimuli despite interference with conduction in A-fibers by anodal current. 7. The cells investigated were located either in the marginal zone or in the layers of the dorsal horn equivalent to Rexed's laminae IV-VI in the cat. The cells were generally activated antidromically from the caudal part of the ventral posterior lateral nucleus of the thalamus.

scholarly journals An ultrafast system for signaling mechanical pain in human skin

2019 ◽  
Vol 5 (7) ◽  
pp. eaaw1297 ◽  
Author(s):  
Saad S. Nagi ◽  
Andrew G. Marshall ◽  
Adarsh Makdani ◽  
Ewa Jarocka ◽  
Jaquette Liljencrantz ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Human Skin ◽  
Single Unit ◽  
High Threshold ◽  
Mechanical Stimuli ◽  
Loss Of Function ◽  
Conduction Velocities ◽  
Low Threshold ◽  
Healthy Participants ◽  
Stimulation Of

The canonical view is that touch is signaled by fast-conducting, thickly myelinated afferents, whereas pain is signaled by slow-conducting, thinly myelinated (“fast” pain) or unmyelinated (“slow” pain) afferents. While other mammals have thickly myelinated afferents signaling pain (ultrafast nociceptors), these have not been demonstrated in humans. Here, we performed single-unit axonal recordings (microneurography) from cutaneous mechanoreceptive afferents in healthy participants. We identified A-fiber high-threshold mechanoreceptors (A-HTMRs) that were insensitive to gentle touch, encoded noxious skin indentations, and displayed conduction velocities similar to A-fiber low-threshold mechanoreceptors. Intraneural electrical stimulation of single ultrafast A-HTMRs evoked painful percepts. Testing in patients with selective deafferentation revealed impaired pain judgments to graded mechanical stimuli only when thickly myelinated fibers were absent. This function was preserved in patients with a loss-of-function mutation in mechanotransduction channel PIEZO2. These findings demonstrate that human mechanical pain does not require PIEZO2 and can be signaled by fast-conducting, thickly myelinated afferents.

Characterization and expression analysis of E75 during ovarian development and juvenile growth of the mud crab, Scylla paramamosain Estampador, 1950 (Brachyura, Portunidae)

Crustaceana ◽  
2019 ◽  
Vol 92 (9) ◽  
pp. 1063-1079
Author(s):  
Jie Gong ◽  
Wenyuan Shi ◽  
Ming Zhang ◽  
Tianfa Wang ◽  
Kun Yu ◽  
...  
Keyword(s):  
Ovarian Development ◽  
Somatic Growth ◽  
Nuclear Hormone Receptor ◽  
Scylla Paramamosain ◽  
Pcr Analysis ◽  
In Vivo Experiments ◽  
Physiological Processes ◽  
Vitellogenic Stage

Abstract In arthropods, E75 is an important nuclear receptor to regulate various physiological processes, such as development and reproduction. In this study, a 3551 bp cDNA of E75 (SpE75) with a typical domain organization of the nuclear hormone receptor was cloned from Scylla paramamosain. A qRT-PCR analysis revealed that, during ovarian development, the expression of SpE75 significantly increased after the onset of vitellogenesis and reached its peak value at the early vitellogenic stage. In vitro and in vivo experiments showed that 20-hydroxyecdysone significantly induced the transcriptions of the genes of both SpE75 and vitellogenin in the ovary. During juvenile crab (C1) development, the expression of SpE75 increased from 0 h (postmoult stage) to 96 h (premoult stage) and kept a low level in the fasting crabs. Together, these results indicate that SpE75 may be playing an important role in the regulation of ovarian development and somatic growth, as a component of ecdysone signalling in crustaceans.

scholarly journals Caenorhabditis elegans PIEZO Channel Coordinates Multiple Reproductive Tissues to Govern Ovulation

2019 ◽  
Author(s):  
Xiaofei Bai ◽  
Jeff Bouffard ◽  
Avery Lord ◽  
Katherine Brugman ◽  
Paul W. Sternberg ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Ion Channels ◽  
Calcium Signaling ◽  
Brood Size ◽  
Mechanical Stimuli ◽  
C Elegans ◽  
Reproductive Tissues ◽  
Physiological Processes ◽  
Wide Range

AbstractThe PIEZO proteins are involved in a wide range of developmental and physiological processes. Human PIEZO1 and PIEZO2 are newly identified excitatory mechano-sensitive proteins; they are non-selective ion channels that exhibit a preference for calcium in response to mechanical stimuli. To further understand the function of these proteins, we investigated the roles of pezo-1, the sole PIEZO ortholog in C. elegans. pezo-1 is expressed throughout development in C. elegans, with strong expression in reproductive tissues. A number of deletion alleles as well as a putative gain-of-function mutant caused severe defects in reproduction. A reduced brood size was observed in the strains depleted of PEZO-1. In vivo observations show that oocytes undergo a variety of transit defects as they enter and exit the spermatheca during ovulation. Post ovulation oocytes were frequently damaged during spermathecal contraction. Calcium signaling in the spermatheca is normal during ovulation in pezo-1 mutants, however, pezo-1 interacts genetically with known regulators of calcium signaling. Lastly, loss of PEZO-1 caused defective sperm navigation after being pushed out of the spermatheca during ovulation. Mating with males rescued these reproductive deficiencies in our pezo-1 mutants. These findings suggest that PEZO-1 may act in different reproductive tissues to promote proper ovulation and fertilization in C. elegans.

Molecular cloning, expression profiling of a carboxylesterase gene and its potential role in methyl farnesoate degradation in Eriocheir sinensis (Brachyura, Varunidae)

Crustaceana ◽  
2021 ◽  
Vol 94 (9) ◽  
pp. 1085-1101
Author(s):  
Xilei Li ◽  
Tiantian Chen ◽  
Ruihan Xu ◽  
Qiming Xie ◽  
Shiping Su ◽  
...  
Keyword(s):  
Eriocheir Sinensis ◽  
Methyl Farnesoate ◽  
Specific Expression ◽  
Eyestalk Ablation ◽  
In Vivo Experiments ◽  
Physiological Processes ◽  
Potential Applications ◽  
Ablation Experiment

Abstract In crustaceans, methyl farnesoate (MF) is an important sesquiterpenoid to regulate many physiological processes, especially reproduction and ovarian maturation. In this study, a 1919 bp cDNA of carboxylesterases (Es-CXE6) with some conserved motifs of the CXE multifunctional enzyme family was cloned from Eriocheir sinensis. Tissue and stage-specific expression results suggested that Es-CXE6 expression in hepatopancreas was highest and associated with the haemolymph MF titer. In vitro and in vivo experiments showed that Es-CXE6 expression was significantly upregulated by MF treatment in the hepatopancreas but not in the ovary. Furthermore, an eyestalk ablation experiment showed that Es-CXE6 expression was significantly upregulated on days 1 and 3 post eyestalk ablation in the hepatopancreas. Together, these results indicate that Es-CXE6 may degrade MF in the hepatopancreas in E. sinensis. Our results offer a potential approach to maintain the MF titer at appropriate levels, which has potential applications in crab aquaculture.

Platelet Microtubules in Clot Structure Formation and Contractile Force Generation: Investigation of a Controversy

1986 ◽  
Vol 56 (01) ◽  
pp. 023-027 ◽  
Author(s):  
C J Jen ◽  
L V McIntire
Keyword(s):  
Network Formation ◽  
Contractile Force ◽  
Second Phase ◽  
Clot Retraction ◽  
Forming Process ◽  
Microtubule Organization ◽  
Physiological Processes ◽  
Fibrin Network ◽  
Two Parameters

SummaryWhether platelet microtubules are involved in clot retraction/ contraction has been controversial. To address this question we have simultaneously measured two clotting parameters, clot structural rigidity and isometric contractile force, using a rheological technique. For recalcified PRP clots these two parameters began rising together at about 15 min after CaCl2 addition. In the concentration range affecting microtubule organization in platelets, colchicine, vinca alkaloids and taxol demonstrated insignificant effects on both clotting parameters of a recalcified PRP clot. For PRP clots induced by adding small amounts of exogenous thrombin, the kinetic curves of clot rigidity were biphasic and without a lag time. The first phase corresponded to a platelet-independent network forming process, while the second phase corresponded to a platelet-dependent process. These PRP clots began generating contractile force at the onset of the second phase. For both rigidity and force parameters, only the second phase of clotting kinetics was retarded by microtubule affecting reagents. When PRP samples were clotted by adding a mixture of CaCl2 and thrombin, the second phase clotting was accelerated and became superimposed on the first phase. The inhibitory effects of micro tubule affecting reagents became less pronounced. Thrombin clotting of a two-component system (washed platelets/ purified fibrinogen) was also biphasic, with the second phase being microtubule-dependent. In conclusion, platelet microtubules are important in PRP clotted with low concentrations of thrombin, during which fibrin network formation precedes platelet-fibrin interactions. On the other hand they are unimportant if a PRP clot is induced by recalcification, during which the fibrin network is constructed in the presence of platelet-fibrin interactions. The latter is likely to be more analogous to physiological processes in vivo.

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