Abstract：
:Measurements of affinity and efficacy are fundamental for work on agonists both in drug discovery and in basic studies on receptors. In this review I wish to consider methods for measuring affinity and efficacy at G protein coupled receptors (GPCRs). Agonist affinity may be estimated in terms of the dissociation constant for agonist binding to a receptor using ligand binding or functional assays. It has, however, been suggested that measurements of affinity are always contaminated by efficacy so that it is impossible to separate the two parameters. Here I show that for many GPCRs, if receptor/G protein coupling is suppressed, experimental measurements of agonist affinity using ligand binding (K(obs)) provide quite accurate measures of the agonist microscopic dissociation constant (KA). Also in pharmacological functional studies, good estimates of agonist dissociation constants are possible. Efficacy can be quantitated in several ways based on functional data (maximal effect of the agonist (E(max)), ratio of agonist dissociation constant to concentration of agonist giving half maximal effect in functional assay (K(obs)/EC50), a combined parameter E(max)K(obs)/EC50). Here I show that E(max)K(obs)/EC50 provides the best assessment of efficacy for a range of agonists across the full range of efficacy for full to partial agonists. Considerable evidence now suggests that ligand efficacy may be dependent on the pathway used to assess it. The efficacy of a ligand may, therefore, be multidimensional. It is still, however, necessary to have accurate measures of efficacy in different pathways.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Strange PGdoi
10.1038/sj.bjp.0707672subject
Has Abstractpub_date
2008-04-01 00:00:00pages
1353-63issue
7eissn
0007-1188issn
1476-5381pii
0707672journal_volume
153pub_type
杂志文章,评审abstract：:The non-peptide NK1 receptor antagonist, CP-96,345, and its 2R,3R enantiomer CP-96,344, which is not an NK1 receptor antagonist (IC50 > 10 microM), were evaluated for antinociceptive and anti-inflammatory activities in several classical models of pain and inflammation in the rat. Both CP-96,345 and CP-96,344 reduced c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb12737.x
更新日期：1992-10-01 00:00:00
abstract：:1 Anthopleurin-B (AP-B, greater than 3 x 10(-9) M), a newly isolated polypeptide from sea anemone (Anthopleura xanthogrammica), caused powerful rhythmic contractions in the guinea-pig isolated vas deferens. The other polypeptides anthopleurin-A from A. xanthogrammica and anthopleurin-C from A. elegantissima, elicited ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1981.tb09951.x
更新日期：1981-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:In humans and non-human primates, the 7TM receptor GPR17 exists in two isoforms differing only by the length of the N-terminus. Of these, only the short isoform has previously been characterized. Hence, we investigated gene expression and ligand-binding profiles of both splice variants and furthe...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00633.x
更新日期：2010-03-01 00:00:00
abstract：:The aim of the present study was to investigate the contribution of bradykinin (BK) B(1) and B(2) receptors in a model of type III hypersensitivity, the reverse passive Arthus reaction (RPA), in wild-type mice and transgenic B(2) knockout littermates. BK (10 microg mouse(-1)) or bovine serum albumin (0.5 mg mouse(-1))...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703225
更新日期：2000-04-01 00:00:00
abstract：:1. The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5 ml min-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostagl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15307.x
更新日期：1996-04-01 00:00:00
abstract：:1. Taxanes are antineoplastic drugs which have cardiovascular side effects of unknown mechanism. We investigated their influence on blood viscosity and erythrocyte morphology. 2. Whole blood was incubated in vitro with increasing concentrations of Taxol, Taxotere, paclitaxel (0-100 microM) and the vehicles Cremophor-E...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704387
更新日期：2001-11-01 00:00:00
abstract：:1 The concept that presynaptic receptors regulate noradrenergic transmitter release via a system of inhibitory receptors mediating negative feedback relies on a supposed association between increases in stimulation-induced efflux of [3H]-noradrenaline by antagonists and blockade by them of the inhibitory effects of ex...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1982.tb09308.x
更新日期：1982-10-01 00:00:00
abstract：:1. The purpose of this investigation was to examine the outputs of peptide histidine isoleucine (PHI) and vasoactive intestinal peptide (VIP) from the gastric corpus in response to stimulation of the peripheral (PVS) and central (CVS) ends of the vagus nerve and to compare the effects of PHI on gastric motility and bl...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb15787.x
更新日期：1990-06-01 00:00:00
abstract：:1. Chronic benzodiazepine administration has been associated with tolerance and with downregulation of gamma-aminobutyric acidA (GABAA)-receptor binding and function. However, effects of individual benzodiazepines on brain regions have varied. 2. To compare the effects of chronic lorazepam and alprazolam, we have admi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb14167.x
更新日期：1990-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Imiquimod is an immunomodulator approved for the treatment of basal cell carcinoma and has adverse side effects, including taste disturbances. Paracrine transmission, representing cell-cell communication within taste buds, has the potential to shape the final signals that taste buds transmit to t...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13567
更新日期：2016-11-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice. EXPERIMENTAL APPROACH:Effects of short-term treatmen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00145.x
更新日期：2009-06-01 00:00:00
abstract：:1. The effect of trimebutine on the voltage-dependent inward Ca2+ current was investigated by the whole-cell voltage-clamp technique in single smooth muscle cells from rabbit ileum. 2. Trimebutine (3-100 microM) reduced the Ca2+ current in a concentration-dependent manner. The inhibitory effect on the Ca2+ current was...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13823.x
更新日期：1993-09-01 00:00:00
abstract：:Initiation of 60 min ischaemia to rat isolated hearts produced a depression in developed tension and heart rate. Subsequent reperfusion caused a greatly exacerbated creatine phosphokinase (CPK) efflux and limited functional recovery. Sulphinpyrazone (100 ng ml-1 and 1 microgram ml-1) significantly reduced CPK release,...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1984.tb10138.x
更新日期：1984-09-01 00:00:00
abstract：:Proteinase-activated receptor-2 (PAR-2) is expressed throughout the gastrointestinal tract including the pancreas, and may be involved in digestive functions. The aim of our study was to evaluate a potential role for PAR-2 in regulating salivary and pancreatic exocrine secretion in vivo. PAR-2-activating peptides (PAR...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703274
更新日期：2000-04-01 00:00:00
abstract：:Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2008.00085.x
更新日期：2009-03-01 00:00:00
abstract：:1 alpha-Monofluoromethyldopa (MFMD, RMI 71963), a potent and selective enzyme-activated irreversible inhibitor of aromatic L-amino acid decarboxylase produces a substantial and long-lasting decrease in the catecholamine content of mouse brain, heart and kidney. 2 Single doses of MFMD reduce the 5-hydroxytryptamine con...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb09776.x
更新日期：1980-12-01 00:00:00
abstract：:1. We have taken advantage of our recent development of highly potent and specific phosphinic inhibitors of endopeptidase 3.4.24.15 to examine the putative contribution of the enzyme in the secretion of A beta by HK293 transfected cells overexpressing the wild type and the Swedish (Sw) double mutated form of beta APP7...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701151
更新日期：1997-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Partial agonists selective for α4β2 nicotinic ACh receptors have been developed for smoking cessation as they induce weak activation of native α4β2* receptors and inhibit effect of nicotine. However, it is unclear whether at brain functions there is an existence of receptor reserve that allows we...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01628.x
更新日期：2012-02-01 00:00:00
abstract：:1. The electrophysiological effects of prazosin, a highly specific alpha 1-adrenoceptor antagonist, on transmembrane action potential characteristics were studied in guinea-pig papillary muscles. 2. At concentrations between 10(-6) M and 10(-5) M, prazosin produced a concentration-dependent decrease in the maximum ups...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14796.x
更新日期：1994-03-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Strontium ranelate, a drug approved and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium-sensing (CaS) receptor. However, it is not known whether bone-targeted CaS receptor positive allosteric modulators (PAMs; calcimimetics) rep...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14344
更新日期：2018-11-01 00:00:00
abstract：:1. Catecholamine release from cat adrenal glands perfused at a high rate (4 ml min-1) at 37 degrees C with modified Krebs solutions lacking Ca and containing 1.2 mM K (hyperpolarizing solution) or 118 mM K (depolarizing solution) was triggered by 10-s pulses of Ca (0.5 mM) in the presence of 118 mM K. Hyperpolarized g...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11874.x
更新日期：1989-03-01 00:00:00
abstract：:1. Bradykinin (BK) and Lys-BK are peptides which are released at high nanomolar concentrations into the tear-film of ocular allergic patients. We hypothesized that these peptides may activate specific receptors on the ocular surface, especially the corneal epithelium (CE) and thus the CE cells may represent a potentia...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701168
更新日期：1997-06-01 00:00:00
abstract：:1. Two preparations, a segment of the ileum and the myenteric plexuslongitudinal muscle preparation, have been used for an analysis of the inhibitory effects of adrenaline, noradrenaline and isoprenaline on the contractor responses of the longitudinal muscle to acetylcholine or to electrical, coaxial or field, stimula...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb12903.x
更新日期：1970-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The psychostimulant cocaine induces complex molecular, cellular and behavioural responses as a consequence of inhibiting presynaptic dopamine, noradrenaline and 5-HT transporters. To elucidate 5-HT transporter (SERT)-specific contributions to cocaine action, we evaluated cocaine effects in the SE...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13899
更新日期：2017-08-01 00:00:00
abstract：:1. Derivatization of nonsteroidal anti-inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti-inflammatory activity and analgesic potency. In this study, we compared the anti-inflammatory potency of prednisolone to a nitric oxide-releasing der...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705324
更新日期：2003-07-01 00:00:00
abstract：:1. To determine the possible role of Ca(2+)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR), the effects of agents which interact with these channels on tension and 86Rb efflux were compared in endothelium-denuded strips of carotid, femoral and mesen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13465.x
更新日期：1993-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The regulation of vascular soluble guanylyl cyclase (sGC) expression by nitric oxide (NO) is still under discussion. In vitro, NO has been shown to downregulate the expression of sGC but it is unclear if this mechanism is operative in vivo and occurs during nitrate treatment. EXPERIMENTAL APPROA...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/bjp.2008.269
更新日期：2008-10-01 00:00:00
abstract：:1. The GABA-B receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APPi) have antitussive activity in the cat and guinea pig. The purpose of this study was to investigate the sites of action of these GABA-B receptor agonists to inhibit the cough reflex. 2. Single intracerebroventricular (i.c.v.) cannulas wer...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17145.x
更新日期：1994-12-01 00:00:00
abstract：:1. The ratio of the content of vasopressin to that of oxytocin (V/O ratio) was estimated in the supraoptic nucleus (SON), paraventricular nucleus (PVN) and posterior pituitary gland (PIT) of guinea-pigs.2. Extracts were assayed for antidiuretic activity to estimate vasopressin and for milk-ejecting activity to estimat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb06912.x
更新日期：1973-06-01 00:00:00
abstract：:It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with inc...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12960
更新日期：2015-03-01 00:00:00
