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A simple self‐reported adherence tool as a predictor of viral rebound in people with viral suppression on antiretroviral therapy 下载免费PDF全文
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. Oktay H. Cabadak E. skender Z. Gren E. allkan O. Orun N. Aslan A. Karaalp A. Tolun N. B. Ulusoy A. I. Levey E. E. El-Fakahany B. Kan 《Autonomic & autacoid pharmacology》1998,18(4):195-204
1 The affinities of 10 selective muscarinic receptor antagonists against [3H]-quinuclidinyl benzilate (QNB) binding were determined to characterize the muscarinic receptors present in guinea-pig gallbladder smooth muscle. The highest correlation was obtained for the comparison between the pKi values for the gallbladder smooth muscle and M2 sites. Pirenzepine revealed two binding sites with affinities indicating the presence of muscarinic M2 receptors in abundance and a minor population of an additional site(s). 2 Carbachol produced gallbladder contractions, stimulated phosphoinositide (PI) hydrolysis and inhibited cAMP formation concentration-dependently with pD2 values of 6.12 ± 0.11, 5.18 ± 0.33 and 7.19 ± 0.15, respectively. 3 Pirenzepine, 4-DAMP, HHSiD, pF-HHSiD, AF-DX 116, methoctramine, AQ-RA 741, guanylpirenzepine and AF-DX 384 showed competitive antagonism against carbachol-induced gallbladder contractions. There was no correlation between the pA2 values for the gallbladder and pKi values for the M2 sites, whereas significant correlations were found for the M1, M3 and M4 sites, the best correlation being between the pA2 values for the gallbladder and M4 subtypes. 4 Finally, the presence of both m2 and m4 receptor proteins were demonstrated by Western blot analysis. It is concluded that guinea-pig gallbladder smooth muscle has both muscarinic M2 and M4 receptors, which are coupled to adenylate cyclase inhibition and PI hydrolysis. 5 Although it seems likely that M2 receptors do not play a primary role in carbachol-induced guinea-pig gallbladder contraction, the characterization of the muscarinic subtypes which mediate these contractile responses needs further evidence. 相似文献
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Historically, the ability of a ligand to bind to its receptor and the ability to subsequently activate that receptor have been described as the properties of affinity and intrinsic efficacy, respectively. These properties were originally believed to be independent of one another; both are possessed by ligands classed as "agonists," and they have served as the quantitative foundation of the drug and receptor classification process. Although affinity has been interpreted readily in physicochemical terms, equivalent molecular models for efficacy remain elusive. In recent times, there has been a significant paradigm shift in our understanding of the interrelationship between affinity and intrinsic efficacy, particularly on theoretical grounds, yet the actual methods available to measure these parameters remain largely operational. Nevertheless, a number of approaches, based on both functional measurements and radioligand binding studies, are available to quantify agonist efficacy on a relative scale and, to date, these remain the most practical. This commentary discusses the most common of these methods, their advantages and limitations, the dependence of the expression of agonism on the chosen assay system, and the impact of recent biochemical and molecular biological advances on the study of efficacy. Additionally, some of the more contemporary theories regarding the molecular nature of efficacy are briefly discussed, as well as the caveats that always must be borne in mind when any determinations of relative agonist efficacy are made. 相似文献