FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3017103176> ?p ?o ?g. }

• W3017103176 abstract "Phenylephrine, L-erythromethoxamine and metaraminol are selective α1-adrenoceptor agonists having phenethylamine chemical structure and used to treat a variety of clinical conditions, including sepsis, anaesthesia associated hypotension, nasal congestion, haemorrhoids, and the evaluation of eye function. Their action involves activation of α1-adrenoceptor on the smooth muscle of major organs to induce a contraction and the resultant therapeutic benefit is dependent on the maintenance of stable response. The signalling mechanism most closely linked to α1-adrenoceptors in smooth muscle is stimulation of phosphatidylinositol metabolism, which induces subsequent elevation of intracellular calcium ions. Lithium ions are also used clinically in the treatment of bipolar disorders and are known to prevent degradation of a key mediator of phosphoinositide metabolism and there are a few reports suggest that this cation can enhance or maintain contractions mediated by α1-adrenoceptors. In the present study, I have investigated the interaction between lithium ions and constrictor responses to a variety of agonists, including selective α1-adrenoceptor agonists, with a particular focus on both the potency of the constrictor agent and the time course of responses. I have also used pharmacological approaches to better understand the basis of a novel interaction between lithium ions and selective α1-adrenoceptor agonists.Two methods have been employed. Isometric tension recording of isolated vascular and urethral smooth muscle determined using a standard approach of maintaining the tissue in Krebs-Henseliet solution gassed with 95%O2/5%CO2. Agonists were added either cumulatively or as a single concentration and the magnitude and time course of the contraction assessed with lithium and in the presence of selective inhibitors. In addition, the time of course of changes in human skin blood flow, using laser Doppler flowmetry, to the iontophoretic application of phenylephrine has also been evaluated.Our in vitro results show that the contractions of the isolated vascular smooth muscle to KCl and the thromboxane mimetic (U46619), were sustained for up to three hours. In contrast contraction to high concentrations to noradrenaline, 5HT, histamine, vasopressin, angiotensin II, carbachol and the selective α1-adrenoceptor agonist were not. Furthermore, in porcine isolated splenic artery segments, the use of therapeutic concentration of lithium (1mM) increased the maximum response to the selective α1-adrenoceptor agonists (and carbachol) almost 2 fold it did not increase the sensitivity of the tissue to these drugs. In contrast, the time course of responses to noradrenaline, cirazoline, 5HT, histamine, vasopressin and angiotensin II was not affected by lithium. Interestingly, similar interaction was also reported in isolated porcine renal and mesenteric arteries, splenic vein and urethral smooth muscle. Moreover, our results showed that this interaction is sensitive to Ca2+ and abolished in the absence of this cation. This interaction prevents the desensitisation of the receptors which develop following the repetitive exposure to a high concentration of α1-adrenoceptor agonists. Furthermore, we confirm that this synergistic interaction is not related to internalisation, or inhibition of inositol monophosphatase, glycogen synthase kinase, Rho kinase or nitric oxide pathways. Although we reported similar enhancement in the time course of phenylephrine using nM of Na+-K+ ATPase inhibitor (ouabain), the magnitude of the response was much smaller than that reported with lithium. Our in vivo results demonstrate that the time course of contraction induced by iontophoresis of phenylephrine was relatively stable for more than 30 minutes which suggest that the concentrations reaching the superficial blood vessels were low and therefore there was no point of investigating the effect of lithium on the contraction induced by phenylephrine in this system.In conclusion, I have demonstrated that the use of high concentration of phenethylamine derived α1-adrenoceptor agonists synergistically interact with therapeutics concentration of LiCl in various smooth muscle preparations and that phosphoinositide metabolism is not involved. This synergistic effect appeared as sustain in the time course of the contraction induced by these agonists and could be accompanied by an enhancement in the magnitudes of the response. Further clinical studies using different approaches are needed to detect any potential clinical uses of this interaction." @default.
• W3017103176 created "2020-04-24" @default.
• W3017103176 creator A5024453152 @default.
• W3017103176 date "2019-10-15" @default.
• W3017103176 modified "2023-09-27" @default.
• W3017103176 title "Synergistic interaction of lithium ions and α1-adrenoceptor agonists in vascular and non-vascular porcine smooth muscle" @default.
• W3017103176 hasPublicationYear "2019" @default.
• W3017103176 type Work @default.
• W3017103176 sameAs 3017103176 @default.
• W3017103176 citedByCount "0" @default.
• W3017103176 crossrefType "dissertation" @default.
• W3017103176 hasAuthorship W3017103176A5024453152 @default.
• W3017103176 hasConcept C12554922 @default.
• W3017103176 hasConcept C126322002 @default.
• W3017103176 hasConcept C134018914 @default.
• W3017103176 hasConcept C163415756 @default.
• W3017103176 hasConcept C170493617 @default.
• W3017103176 hasConcept C185592680 @default.
• W3017103176 hasConcept C24998067 @default.
• W3017103176 hasConcept C2777952589 @default.
• W3017103176 hasConcept C2778938600 @default.
• W3017103176 hasConcept C2779395532 @default.
• W3017103176 hasConcept C2992686903 @default.
• W3017103176 hasConcept C40465926 @default.
• W3017103176 hasConcept C55493867 @default.
• W3017103176 hasConcept C71924100 @default.
• W3017103176 hasConcept C84393581 @default.
• W3017103176 hasConcept C86803240 @default.
• W3017103176 hasConcept C98274493 @default.
• W3017103176 hasConceptScore W3017103176C12554922 @default.
• W3017103176 hasConceptScore W3017103176C126322002 @default.
• W3017103176 hasConceptScore W3017103176C134018914 @default.
• W3017103176 hasConceptScore W3017103176C163415756 @default.
• W3017103176 hasConceptScore W3017103176C170493617 @default.
• W3017103176 hasConceptScore W3017103176C185592680 @default.
• W3017103176 hasConceptScore W3017103176C24998067 @default.
• W3017103176 hasConceptScore W3017103176C2777952589 @default.
• W3017103176 hasConceptScore W3017103176C2778938600 @default.
• W3017103176 hasConceptScore W3017103176C2779395532 @default.
• W3017103176 hasConceptScore W3017103176C2992686903 @default.
• W3017103176 hasConceptScore W3017103176C40465926 @default.
• W3017103176 hasConceptScore W3017103176C55493867 @default.
• W3017103176 hasConceptScore W3017103176C71924100 @default.
• W3017103176 hasConceptScore W3017103176C84393581 @default.
• W3017103176 hasConceptScore W3017103176C86803240 @default.
• W3017103176 hasConceptScore W3017103176C98274493 @default.
• W3017103176 hasLocation W30171031761 @default.
• W3017103176 hasOpenAccess W3017103176 @default.
• W3017103176 hasPrimaryLocation W30171031761 @default.
• W3017103176 hasRelatedWork W1573626680 @default.
• W3017103176 hasRelatedWork W1964558223 @default.
• W3017103176 hasRelatedWork W1967717701 @default.
• W3017103176 hasRelatedWork W1976047381 @default.
• W3017103176 hasRelatedWork W2003418340 @default.
• W3017103176 hasRelatedWork W2059936150 @default.
• W3017103176 hasRelatedWork W2064225076 @default.
• W3017103176 hasRelatedWork W2067369444 @default.
• W3017103176 hasRelatedWork W2140451057 @default.
• W3017103176 hasRelatedWork W2184406981 @default.
• W3017103176 hasRelatedWork W2184471628 @default.
• W3017103176 hasRelatedWork W2263545522 @default.
• W3017103176 hasRelatedWork W2273051204 @default.
• W3017103176 hasRelatedWork W2311393071 @default.
• W3017103176 hasRelatedWork W2399553190 @default.
• W3017103176 hasRelatedWork W2403536483 @default.
• W3017103176 hasRelatedWork W2415404974 @default.
• W3017103176 hasRelatedWork W2421731426 @default.
• W3017103176 hasRelatedWork W2425106212 @default.
• W3017103176 hasRelatedWork W2462799222 @default.
• W3017103176 isParatext "false" @default.
• W3017103176 isRetracted "false" @default.
• W3017103176 magId "3017103176" @default.
• W3017103176 workType "dissertation" @default.