scholarly journals The α1-adrenoceptor inhibitor ρ-TIA facilitates net hunting in piscivorous Conus tulipa

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Mriga Dutt ◽  
Jean Giacomotto ◽  
Lotten Ragnarsson ◽  
Åsa Andersson ◽  
Andreas Brust ◽  
...  

AbstractCone snails use separately evolved venoms for prey capture and defence. While most use a harpoon for prey capture, the Gastridium clade that includes the well-studied Conus geographus and Conus tulipa, have developed a net hunting strategy to catch fish. This unique feeding behaviour requires secretion of “nirvana cabal” peptides to dampen the escape response of targeted fish allowing for their capture directly by mouth. However, the active components of the nirvana cabal remain poorly defined. In this study, we evaluated the behavioural effects of likely nirvana cabal peptides on the teleost model, Danio rerio (zebrafish). Surprisingly, the conantokins (NMDA receptor antagonists) and/or conopressins (vasopressin receptor agonists and antagonists) found in C. geographus and C. tulipa venom failed to produce a nirvana cabal-like effect in zebrafish. In contrast, low concentrations of the non-competitive adrenoceptor antagonist ρ-TIA found in C. tulipa venom (EC50 = 190 nM) dramatically reduced the escape response of zebrafish larvae when added directly to aquarium water. ρ-TIA inhibited the zebrafish α1-adrenoceptor, confirming ρ-TIA has the potential to reverse the known stimulating effects of norepinephrine on fish behaviour. ρ-TIA may act alone and not as part of a cabal, since it did not synergise with conopressins and/or conantokins. This study highlights the importance of using ecologically relevant animal behaviour models to decipher the complex neurobiology underlying the prey capture and defensive strategies of cone snails.

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3321 ◽  
Author(s):  
Jinlan Lu ◽  
Ling Liu ◽  
Xingyu Zhu ◽  
Li Wu ◽  
Zhipeng Chen ◽  
...  

Qing’e Pills is a Chinese traditional herbal product, which is often used to strengthen muscles and bones in TCM (traditional Chinese Medicine) practice. Its two main component herbs, namely, Cortex Eucommiae and Fructus Psoraleae are both required to be salt-fried according to TCM theory. We have evaluated the effects of salt-frying treated herbs on Caco-2 cell uptake behavior for those active ingredients of Qing’e Pills. By investigating of various variables, including MTT, temperature, inhibitors, pH, salt concentration and herb processing methods, we tried to clarify whether the salt-processing on herbs was necessary or not. Results showed that, compared to other processing methods, the salt-frying process significantly (p < 0.01) enhanced the absorption of effective components of Qing’e Pills. The way that psoralen, isopsoralen, psoralenoside and geniposide acid entered Caco-2 cells at low concentrations was via passive diffusion. These components were not substrates of P-glycoprotein. It demonstrated that the salt-frying process not only enhanced the concentration of active components in herb extract, but also changed their absorption behaviors. Nevertheless, the mechanism of absorption behavior changing needs to be further investigated.


Author(s):  
Hadeel A. Alsufyani ◽  
James R. Docherty

Contractions of rat portal vein in response to the α1-adrenoceptor agonist phenylephrine consist of phasic contractions at low concentrations, with tonic contractions superimposed at higher concentrations. The α1D-adrenoceptor antagonist BMY7378 (7.0, -log M) did not affect phasic or tonic contractions to phenylephrine. The relatively non-selective α1-adrenoceptor antagonist prazosin (7.5) shifted equally the potencies of phenylephrine at producing phasic and tonic contractions, with pKB values of 8.85 and 8.83 (-log M), respectively. The α1A-adrenoceptor antagonist RS100329 (8.5) produced a significantly greater shift in phenylephrine potency for phasic (pKB of 10.51) than tonic contractions (pKB of 9.78). Prazosin was less effective than RS100329 at reducing the effects of phenylphrine on frequency of phasic contractions. The Rho kinase inhibitor fasudil (5.0) did not affect phasic contractions to phenylephrine, but significantly reduced tonic contractions. It is concluded that there is no evidence for involvement of α1D-adrenoceptors in responses of rat portal vein to phenylephrine, but phasic responses involve predominantly α1A-adrenoceptors. Tonic responses may involve predominantly α1B-adrenoceptors, and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil.


1988 ◽  
Vol 254 (2) ◽  
pp. R277-R283 ◽  
Author(s):  
G. P. Matherne ◽  
K. T. Nakamura ◽  
J. E. Robillard

The renal hemodynamic response to renal arterial infusions of guanabenz (alpha 2-adrenoceptor agonist) and phenylephrine (alpha 1-adrenoceptor agonist) were compared in conscious and chronically instrumented fetal (132-140 days gestation; term 145 days), newborn (6-15 days postnatal), and nonpregnant adult sheep. Phenylephrine produced similar dose-related decreases in renal blood flow velocity in all three groups at low concentrations (less than 1.8 X 10(-7) M) of drug in renal blood, whereas at the highest concentration adults demonstrated the most vasoconstriction and newborns the least (P less than 0.05 ANOVA). Responses to phenylephrine infusion during renal alpha 1-adrenoceptor blockade with prazosin were completely inhibited. Guanabenz produced greater renal vasoconstriction in adult sheep (P less than 0.05 ANOVA) at all concentrations (0.6 X 10(-6) to 8 X 10(-6) M) when compared with fetal and newborn sheep. Guanabenz-mediated vasoconstriction was not affected by alpha 1-adrenoceptor blockade with prazosin but was completely inhibited by the addition of an alpha 2-adrenoceptor antagonist idazoxan. Results of the present study demonstrate that renal vasoconstriction is mediated by both alpha 1- and alpha 2-adrenoceptors in fetal, newborn, and adult sheep. Moreover, these results suggest that renal alpha 1- and alpha 2-adrenoceptor-mediated vasoconstrictor responses mature at different rates.


2019 ◽  
Vol 7 (3) ◽  
pp. 600-608 ◽  
Author(s):  
Qi Shi ◽  
Yongjun Ji ◽  
Wenxin Chen ◽  
Yongxia Zhu ◽  
Jing Li ◽  
...  

Abstract Single-atom catalysts are of great interest because they can maximize the atom-utilization efficiency and generate unique catalytic properties; however, much attention has been paid to single-site active components, rarely to catalyst promoters. Promoters can significantly affect the activity and selectivity of a catalyst, even at their low concentrations in catalysts. In this work, we designed and synthesized CuO catalysts with atomically dispersed co-promoters of Sn and Zn. When used as the catalyst in the Rochow reaction for the synthesis of dimethyldichlorosilane, this catalyst exhibited much-enhanced activity, selectivity and stability compared with the conventional CuO catalysts with promoters in the form of nanoparticles. Density functional theory calculations demonstrate that single-atomic Sn substitution in the CuO surface can enrich surface Cu vacancies and promote dispersion of Zn to its atomic levels. Sn and Zn single sites as the co-promoters cooperatively generate electronic interaction with the CuO support, which further facilitates the adsorption of the reactant molecules on the surface, thereby leading to the superior catalytic performance.


2015 ◽  
Vol 86 (1) ◽  
pp. 58-74 ◽  
Author(s):  
Baldomero M. Olivera ◽  
Jon Seger ◽  
Martin P. Horvath ◽  
Alexander E. Fedosov

The venomous fish-hunting cone snails (Conus) comprise eight distinct lineages evolved from ancestors that preyed on worms. In this article, we attempt to reconstruct events resulting in this shift in food resource by closely examining patterns of behavior, biochemical agents (toxins) that facilitate prey capture and the combinations of toxins present in extant species. The first sections introduce three different hunting behaviors associated with piscivory: ‘taser-and-tether', ‘net-engulfment' and ‘strike-and-stalk'. The first two fish-hunting behaviors are clearly associated with distinct groups of venom components, called cabals, which act in concert to modify the behavior of prey in a specific manner. Derived fish-hunting behavior clearly also correlates with physical features of the radular tooth, the device that injects these biochemical components. Mapping behavior, biochemical components and radular tooth features onto phylogenetic trees shows that fish-hunting behavior emerged at least twice during evolution. The system presented here may be one of the best examples where diversity in structure, physiology and molecular features were initially driven by particular pathways selected through behavior.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. W. A. Himaya ◽  
Ai-Hua Jin ◽  
Brett Hamilton ◽  
Subash K. Rai ◽  
Paul Alewood ◽  
...  

AbstractThe venom duct origins of predatory and defensive venoms has not been studied for hook-and-line fish hunting cone snails despite the pharmacological importance of their venoms. To better understand the biochemistry and evolution of injected predatory and defensive venoms, we compared distal, central and proximal venom duct sections across three specimens of C. striatus (Pionoconus) using proteomic and transcriptomic approaches. A total of 370 conotoxin precursors were identified from the whole venom duct transcriptome. Milked defensive venom was enriched with a potent cocktail of proximally expressed inhibitory α-, ω- and μ-conotoxins compared to milked predatory venom. In contrast, excitatory κA-conotoxins dominated both the predatory and defensive venoms despite their distal expression, suggesting this class of conotoxin can be selectively expressed from the same duct segment in response to either a predatory or defensive stimuli. Given the high abundance of κA-conotoxins in the Pionoconus clade, we hypothesise that the κA-conotoxins have evolved through adaptive evolution following their repurposing from ancestral inhibitory A superfamily conotoxins to facilitate the dietary shift to fish hunting and species radiation in this clade.


2022 ◽  
Vol 6 (2) ◽  
pp. 01-03
Author(s):  
Wasan Mohammed Alsewidi

Many studies determined effect of plant extract on plant pathogens and human pathogens. Alhagi maurorum is considered as one of the important medicinal plants in Iraq. It is used for urinary tract infection, rheumatic pains and liver disorders. Study the Inhibition Effect of Alhagi extract on oral microorganisms as Streptococci, Actinobacillus and Staphylococci, with (0, 10, 50 and 100 percentages). The concentrations of 0% has not any inhibition effect, 10%, has a slight inhibition effect against oral Streptococci and Actinobacillus, but has not effect on Staphylococci. 50%, has an inhibition effect against oral Streptococci more than E-coli, but has not effect on Staphylococci, but 100%, has a wide inhibition effect a against oral Streptococci more than Actinobacillus except Staphylococci has not effect. The lack of inhibition effect at the concentration of 0% and 10% of Alhagi maurorum aqueous extract may be returned to the limits or decline of active components in these low concentrations of aqueous extract. In addition, studies indicate that there are many factors have an effect in the minimizing the impact of plant extracts.


2000 ◽  
Vol 203 (3) ◽  
pp. 559-565 ◽  
Author(s):  
T. Preuss ◽  
W.F. Gilly

Although extensively used for biophysical studies, the squid giant axon system remains largely unexplored in regard to in vivo function and modulation in any biologically relevant context. Here we show that successful establishment of the recruitment pattern for the giant axon in the escape response elicited by a brief electrical stimulus depends on prey-capture experience early in life. Juvenile squid fed only slow-moving, easy-to-capture prey items (Artemia salina) develop deficits in coordinating activity in the giant axon system with that of a parallel set of non-giant motor axons during escape responses. These deficits are absent in cohorts fed fast-moving, challenging prey items (copepods). These results suggest that the acquisition of inhibitory control over the giant axon system is experience-dependent and that both prey-capture and escape behavior depend on this control.


2015 ◽  
Vol 112 (6) ◽  
pp. 1743-1748 ◽  
Author(s):  
Helena Safavi-Hemami ◽  
Joanna Gajewiak ◽  
Santhosh Karanth ◽  
Samuel D. Robinson ◽  
Beatrix Ueberheide ◽  
...  

More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail’s distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.


2017 ◽  
Vol 13 (12) ◽  
pp. 2453-2465 ◽  
Author(s):  
Jutty Rajan Prashanth ◽  
Sebastien Dutertre ◽  
Richard James Lewis

Cone snails use distinct venoms for defence and prey capture. The pharmacology of these neurotoxic peptides have been extensively studied for pharmacological probes, venom evolution mechanisms and potential therapeutics.


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