Search results for "adrenoceptor"

Cardiac and vascular alpha(1)-adrenoceptors in congestive heart failure: a systematic review

2020

As heart failure (HF) is a devastating health problem worldwide, a better understanding and the development of more effective therapeutic approaches are required. HF is characterized by sympathetic system activation which stimulates α- and β-adrenoceptors (ARs). The exposure of the cardiovascular system to the increased locally released and circulating levels of catecholamines leads to a well-described downregulation and desensitization of β-ARs. However, information on the role of α-AR is limited. We have performed a systematic literature review examining the role of both cardiac and vascular α1-ARs in HF using 5 databases for our search. All three α1-AR subtypes (α1A, α1B and α1D) are exp…

Relaxation by β3-adrenoceptor agonists of the isolated human internal anal sphincter

2009

In this study, responses of beta(3)-adrenoceptor agonists were examined on human isolated internal anal sphincter (IAS) in order to explore their relaxant effects on hypertonicity of IAS.The relaxant efficacy (E(max)) and potency (-logIC(50)) of BRL37344 and SR58611A, beta(3)-adrenoceptor agonists, were examined in contracted IAS muscle strips. The presence of beta(3)-adrenoceptors, and changes in intracellular calcium and cyclic nucleotide levels in IAS muscle were tested by Western blotting, epifluorescence microscopy and enzyme immunoassay, respectively.BRL37344 and SR58611A relaxed contracted IAS muscle (E(max)=27+/-3% and 35+/-3%; -logIC(50)=6.26+/-0.24 and 4.87+/-0.13; respectively). …

Analysis of basic drugs by liquid chromatography with environmentally friendly mobile phases in pharmaceutical formulations

2017

Abstract Basic drugs are positively charged in the usual working pH (2–8) in reversed-phase liquid chromatography. This gives rise to a strong association with the residual ionized silanols in conventional silica-based stationary phases, which is translated in poor peak shape and high consumption of organic solvent to get appropriate retention times. Micellar mobile phases containing surfactants give rise to modified stationary phases, where silanols are masked, improving the peak shape. However, mobile phases containing the anionic surfactant sodium dodecyl sulfate (SDS) require a small amount of organic solvent to conveniently decrease the retention of cationic analytes. An alternative is…

A systematic review of inverse agonism at adrenoceptor subtypes

2020

As many, if not most, ligands at G protein-coupled receptor antagonists are inverse agonists, we systematically reviewed inverse agonism at the nine adrenoceptor subtypes. Except for β3-adrenoceptors, inverse agonism has been reported for each of the adrenoceptor subtypes, most often for β2-adrenoceptors, including endogenously expressed receptors in human tissues. As with other receptors, the detection and degree of inverse agonism depend on the cells and tissues under investigation, i.e., they are greatest when the model has a high intrinsic tone/constitutive activity for the response being studied. Accordingly, they may differ between parts of a tissue, for instance, atria vs. ventricles…

Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex.

1999

The selectivity of 3-nitrosoboldine and different halogenated derivatives of boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was inhibited completely by all the compounds tested. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components. The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3-bromoboldine = 3,8-dibromoboldine = 3-chloroboldineboldine3-nitrosoboldine. The competition curves for 3-bromoboldine remained shallow and biph…

Evaluation and synthesis of 7-arylhydroxymethyltriazolopyridines as potential cardiovascular agents

2002

7-Arylhydroxymethyltriazolopyridines 3a-c and 4a-d were synthesized by regioselective lithiation of [1,2,3]triazolo[1,5-a]pyridines 1 and 2 and subsequent trapping of the 7-lithioderivatives formed using aryl aldehydes as electrophiles. The structural relationship between compounds 3a-c and 4a-d and arylethanolamines suggested their consideration as potential cardiovascular agents. A preliminary evaluation as vascular smooth muscle relaxants was carried out. These compounds did not act as α1-adrenoceptor antagonists and were unable to block calcium entry through voltage-dependent calcium channels. Abarca Gonzalez, Belen, Belen.Abarca@uv.es ; Ballesteros Campos, Rafael, Rafael.Ballesteros@uv…

Editorial Comment from Dr Michel to Expression and functional role of β3-adrenoceptors in the human ureter

2013

Distribución, función y vías de señalización de los adrenoceptores β a nivel vascular

2014

Se ha analizado la contribución de los diferentes subtipos de adrenoceptores (AR) β (β1, β2 β3) en la vasodilatación, determinando su localización en las diferentes células vasculares y evaluando la implicación de las vías de señalización adenilato ciclasa (AC)/AMPc/PKA y/o NO/guanilato ciclasa soluble (GCs)/GMPc, en dos lechos vasculares representantes de: los vasos de resistencia, como la arteria mesentérica de resistencia (A.M.R.) de rata, y de conductancia, como la aorta de rata. Los resultados obtenidos muestran que, a pesar de que los tres subtipos de AR β se expresan en ambos vasos, su participación en la respuesta funcional, así como la vía de señalización utilizada, es diferente se…

The Odd Sibling: Features ofβ3-Adrenoceptor Pharmacology

2014

beta(3)-Adrenoceptor agonists have recently been introduced for the treatment of overactive urinary bladder syndrome. Their target, the beta(3)-adrenoceptor, was discovered much later than beta(1)- and beta(2)-adrenoceptors and exhibits unique properties which make extrapolation of findings from the other two subtypes difficult and the beta(3)-adrenoceptor a less-understood subtype. This article discusses three aspects of beta(3)-adrenoceptor pharmacology. First, the ligand-recognition profile of beta(3)-adrenoceptors differs considerably from that of the other two subtypes, i.e., many antagonists considered as nonselective actually are beta(3)-sparing, including propranolol or nadolol. Man…

a1D-Adrenoceptors are responsible for the high sensitivity and the slow time-course of noradrenaline-mediated contraction in conductance arteries.

2013

The objective of this study was to determine whether the different time-course characteristics of α1-adrenoceptor-mediated contraction in arteries can be related to the subtypes involved. Contractile responses to noradrenaline (NA) were compared with inositol phosphate accumulation and extracellular signal-regulated kinase (ERK)1/2 phosphorylation after α1-agonist stimuli in the same vessels in the presence or absence of α1-antagonists in rat or in α1-subtype knockout (KO) mice. Aorta, where α1D-AR is the main functional subtype, had higher sensitivity to NA (in respect of inositol phosphate [IP], pERK1/2, and contractile response) than tail artery, where the α1A-adrenoceptor subtype is pre…