Abstract：
:The Secretin family of GPCRs are endocrine peptide hormone receptors that share a common genomic organization and are the subject of a wide variety of alternative splicing. All GPCRs contain a central seven transmembrane domain responsible for transducing signals from the outside of the cell as well as extracellular amino and intracellular carboxyl termini. Members of the Secretin receptor family have a relatively large N-terminus and a variety of lines of evidence support a common mode of ligand binding and a common ligand binding fold. These receptors are best characterized as coupling to intracellular signalling pathways via G(αs) and G(αq) but are also reported to couple to a multitude of other signalling pathways. The intracellular loops are implicated in regulating the interaction between the receptor and heterotrimeric G protein complexes. Alternative splicing of exons encoding both the extracellular N-terminal domain as well as the extracellular loops of some family members has been reported and as expected these splice variants display altered ligand affinity as well as differential activation by endogenous ligands. Various forms of alternative splicing have also been reported to alter intracellular loops 1 and 3 as well as the C-terminus and as one might expect these display differences in signalling bias towards downstream effectors. These diverse pharmacologies require that the physiological role of these splice variants be addressed but should provide unique opportunities for drug design and development.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Furness SG,Wootten D,Christopoulos A,Sexton PMdoi
10.1111/j.1476-5381.2011.01571.xsubject
Has Abstractpub_date
2012-05-01 00:00:00pages
98-109issue
1eissn
0007-1188issn
1476-5381journal_volume
166pub_type
杂志文章,评审abstract：:1. We compared the relaxant effect of pituitary adenylate cyclase activating peptide (PACAP) 1-27 with that of a newly developed PACAP 1-27 analogue, [Arg15,20,21Leu17]-PACAP-Gly-Lys-Arg-NH2, in the guinea-pig trachea and primate bronchi in vitro (n = 4-5). 2. In the guinea-pig trachea precontracted by a submaximally ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701310
更新日期：1997-08-01 00:00:00
abstract：:1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, car...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13286.x
更新日期：1995-02-01 00:00:00
abstract：:Although cyclosporin (CsA) is considered to be the best immunosuppressive molecule in transplantation, it has been suspected to alter mitochondrial respiration of various tissues. We evaluated the acute effect of CsA and its vehicle on maximal oxidative capacity (V(max)) of cardiac, soleus and gastrocnemius muscles of...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704129
更新日期：2001-07-01 00:00:00
abstract：:1. The effect of histamine H1-receptor stimulation on inositol phospholipid hydrolysis has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. Histamine (EC50 = 27 microM) stimulated the accumulation of [3H]-inositol phosphates in DDT1MF-2 cells prelabelled with [3H]-myo-inositol. 2-Thi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13462.x
更新日期：1993-01-01 00:00:00
abstract：:Melatonin receptors are seven transmembrane-spanning proteins belonging to the GPCR superfamily. In mammals, two melatonin receptor subtypes exist - MT1 and MT2 - encoded by the MTNR1A and MTNR1B genes respectively. The current review provides an update on melatonin receptors by the corresponding subcommittee of the I...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.13536
更新日期：2016-09-01 00:00:00
abstract：:Botulinum toxin (Type A) depressed or abolished transmission from postganglionic nerves to smooth muscle of isolated preparations of guinea-pig and mouse vas deferens. The time course of blockade was 2 to 6 times slower than that observed with the same concentration of the same batch of toxin on the rat diaphragm. Spo...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08343.x
更新日期：1973-02-01 00:00:00
abstract：:1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704421
更新日期：2001-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Accumulated evidence suggests that oxidative stress is involved in amyloid beta (Abeta)-induced cognitive dysfunction. Silibinin (silybin), a flavonoid derived from the herb milk thistle (Silybum marianum), has been shown to have antioxidative properties; however, it remains unclear whether silib...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00295.x
更新日期：2009-08-01 00:00:00
abstract：:1. The purpose of this study was to compare the pharmacological properties (i.e. the AV nodal depressant, vasodilator, and inotropic effects) of two AV nodal blocking agents belonging to different drug classes; a novel A1 adenosine receptor (A1 receptor) agonist, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside (CVT-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702287
更新日期：1999-01-01 00:00:00
abstract：:(1) Here, we introduce a beta-casomorphin-5-derived cyclic pentapeptide, cCD-2 (Tyr-cyclo[d-Orn-Tyr(Bzl)-Pro-Gly]), which inhibits the cell growth of a variety of human cancer cell lines. (2) This opioid-derived peptide possesses only low affinity for mu-receptors, but enhances the agonist binding to mu-receptors in v...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705416
更新日期：2003-09-01 00:00:00
abstract：:1. Adenosine 5'-triphosphate (ATP) is known to augment cardiac contractile activity and cause an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in isolated cardiomyocytes. However, no information regarding the ATP-mediated signal transduction in the myocardium in congestive heart failure (CHF) is availab...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705867
更新日期：2005-01-01 00:00:00
abstract：:1. Sodium metabisulphite (MBS) can induce bronchoconstriction in patients with asthma. We investigated the effects of MBS aerosol on bronchial blood velocity (Vbr) and pulmonary resistance in intubated conscious sheep. 2. Bronchial blood velocity was measured by implanting a 20 MHz ultrasonic Doppler flow probe on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb14826.x
更新日期：1994-03-01 00:00:00
abstract：:1. Optimal dipeptide and peptidomimetic drug transport across the intestinal mucosal surface is dependent upon the co-operative functional activity of the di/tripeptide transporter hPepT1 and the Na(+)/H(+) exchanger NHE3. The ability of the anti-absorptive enteric neuropeptide VIP (vasoactive intestinal peptide) to m...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705049
更新日期：2003-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:11β-hydroxysteroid dehydrogenase type I (11β-HSD1), a target for Type 2 diabetes mellitus, converts inactive glucocorticoids into bioactive forms, increasing tissue concentrations. We have compared the pharmacokinetic-pharmacodynamic (PK/PD) relationship of target inhibition after acute and repea...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13251
更新日期：2015-10-01 00:00:00
abstract：:Histamine has been one of the most studied substances in medicine, playing a major role in diverse (patho)physiological processes. It elicits its multifaceted modulatory functions by activating four types of GPCRs, designated as H1-4 . Despite the heterogeneity and the complexity of histamine receptor pharmacology, ma...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.14524
更新日期：2020-02-01 00:00:00
abstract：:1. The mechanisms of action of semotiadil fumarate, a novel Ca2+ antagonist, were examined by measuring the cytosolic Ca2+ level ([Ca2+]i) and force of contraction in porcine coronary arteries, and by determining [3H]-pyrilamine binding to bovine cerebellar membranes. 2. Semotiadil or verapamil (0.1 and 1 microM) inhi...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13345.x
更新日期：1995-03-01 00:00:00
abstract：:1. Metolazone, a new diuretic, was found to be excreted by glomerular filtration and renal tubular secretion.2. The secretory mechanism was antagonized by probenecid but this did not affect the diuretic action of metolazone. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1972.tb08104.x
更新日期：1972-07-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12054
更新日期：2013-04-01 00:00:00
abstract：:The effects of the opioid receptor agonist RX783006 and of the opioid receptor partial agonist (+)-meptazinol have been examined on electrically induced twitch responses of the guinea-pig isolated ileum and of the mouse isolated vas deferens. Log10 concentration-tissue state curves were determined for (+)-meptazinol a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb10246.x
更新日期：1986-07-01 00:00:00
abstract：:The effects of the angiotensin-converting-enzyme inhibitor (ACEI) ramiprilat, the angiotensin II type 1 receptor antagonist (AT(1)A) candesartan, and the combination of both drugs on infarct size (IS) resulting from regional myocardial ischaemia were studied in pigs. Both ACEI and AT(1)A reduce myocardial IS by a brad...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703544
更新日期：2000-09-01 00:00:00
abstract：:1. Vanadium compounds can mimic actions of insulin through alternative signalling pathways. The effects of three organic vanadium compounds were studied in non-ketotic, streptozotocin-diabetic rats: vanadyl acetylacetonate (VAc), vanadyl 3-ethylacetylacetonate (VEt), and bis(maltolato)oxovanadium (VM). A simple inorga...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702311
更新日期：1999-01-01 00:00:00
abstract：UNLABELLED:Sarcoplasmic reticular (SR) Ca(2+) -ATPase (SERCA2a) is central to cardiac electrophysiological and mechanical function. It ensures full diastolic relaxation minimizing delayed after-potentials that would otherwise compromise membrane electrophysiological stability, and optimizes SR Ca(2+) refilling and syst...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章
doi：10.1111/bph.12288
更新日期：2013-10-01 00:00:00
abstract：:1. Sodium nitroprusside, S-nitroso-N-acetyl-D,L-penicillamine, Spermine NONOate and DEA NONOate raised cyclic GMP levels in bovine chromaffin cells in a time and concentration dependent manner with different potencies, the most potent being DEA/NO with an EC50 value of 0.38 +/- 0.02 microM. 2. Measurements of NO relea...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702607
更新日期：1999-06-01 00:00:00
abstract：:1. We studied the ability of nitric oxide (NO) to physiologically antagonize endothelin-1 (ET-1) induced constrictions in human internal mammary artery (IMA). We also investigated the hypothesis that NO interacts directly with ET-receptor binding in human heart and aorta. 2. ET-1 potently contracted IMA (EC(50) 6.86 n...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703834
更新日期：2001-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Muscarinic toxins (MTs) are snake venom peptides named for their ability to interfere with ligand binding to muscarinic acetylcholine receptors (mAChRs). Recent data infer that these toxins may have other G-protein-coupled receptor targets than the mAChRs. The purpose of this study was to systema...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2011.01468.x
更新日期：2011-09-01 00:00:00
abstract：:1. The cyclic analogue of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated. 2. When given intraventricularly, ADTN produced so...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07416.x
更新日期：1975-05-01 00:00:00
abstract：:Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703981
更新日期：2001-04-01 00:00:00
abstract：:The effect of a substance P antagonist, [D-Pro2, D-Trp7,9]-substance P (SPA), on gastric emptying and gastrointestinal transit in the rat was studied in order to elucidate a possible physiological role of endogenous substance P and other tachykinins in gastrointestinal motility. SPA was given by intraperitoneal inject...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1986.tb11144.x
更新日期：1986-11-01 00:00:00
abstract：:1. In urethane-anaesthetized guinea-pigs, under spontaneous respiration, indomethacin (1 mg kg-1 i.v., 10-45 min) approximately doubled the bronchoconstrictor effect (increase in airways resistance, R(aw)) of equieffective doses of histamine and 5-hydroxytryptamine (5-HT), but not that of acetylcholine or leukotriene ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11556.x
更新日期：1988-06-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Patients with diabetes mellitus are reported to show a raised prevalence of mental disorders, which may be reflected in impaired social interaction. However, the mechanisms underlying such impairment in diabetes are unknown. EXPERIMENTAL APPROACH:The present study investigated whether social int...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.15326
更新日期：2021-02-01 00:00:00
