Abstract：
:Primary cultures of rat cerebellar granule cells are shown to possess a high density (283 +/- 48 fmol/mg of protein) of muscarinic receptor sites, defined using N-[3H]methylscopolamine [( 3H]NMS), with a KD of 0.18 +/- 0.01 nM measured after culture in vitro for 7 days. Displacement of specific [3H]NMS binding demonstrated a muscarinic receptor with low affinity for pirenzepine (Ki: 240 nM); further investigation using antagonists, AF-DX 116 and 4-DAMP to discriminate between M2 and M3 receptors respectively, revealed low M2 affinity (Ki: 600 nM) and high M3 affinity (Ki: 2.4 nM), indicative of the M3 receptor subtype. The robust muscarinic receptor stimulation of [3H]inositol phosphate formation, previously observed in these cells, was confirmed. Inhibition of this response followed a similar profile to the binding data, exhibiting weak inhibitory effects for pirenzepine (Ki: 710 nM) and AF-DX 116 (Ki: 5000 nM), but a potent action for 4-DAMP (Ki: 2.4 nM). The opposite profile seen for AF-DX 116 and 4-DAMP is indicative of a M3 receptor subtype expressed on these cells and linked to phosphoinositide hydrolysis. Further studies demonstrated that M3 receptor stimulation caused a rapid, transient increase in the second messenger inositol 1,4,5-trisphosphate, suggesting that potential Ca(2+)-homeostatic and neuromodulatory effects may be mediated by this response.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Whitham EM,Challiss RA,Nahorski SRdoi
10.1016/s0922-4106(05)80017-3keywords:
subject
Has Abstractpub_date
1991-03-25 00:00:00pages
181-9issue
3eissn
0014-2999issn
1879-0712journal_volume
206pub_type
杂志文章abstract：:In isolated strips of human urinary bladder detrusor muscle, ATP, alpha, beta-methylene ATP and P1,P6-diadenosine hexaphosphate caused concentration-dependent contractions. ATP was less potent than the two synthetic purine compounds and gave smaller maximum responses. Responses to ATP, P1,P6-diadenosine hexaphosphate ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90881-9
更新日期：1989-12-12 00:00:00
abstract：:Statin therapy is used ubiquitously to reduce cholesterol levels, and recent studies have revealed statin use may be associated with a reduced risk of inflammatory bowel disease (IBD). A comprehensive assessment of the literature was performed to investigate whether statin use may influence the risk of new-onset IBD. ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.173750
更新日期：2021-01-15 00:00:00
abstract：:This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.07.021
更新日期：2014-10-05 00:00:00
abstract：:Discovery in the early 1990s of caveolin-1, the structural protein responsible for maintaining the ohm shape of caveolae, greatly enhanced investigations to elucidate the role of these little caves in the plasma membrane. Perhaps one of the most important realizations concerning caveolae and caveolin is that these ele...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2008.02.086
更新日期：2008-05-13 00:00:00
abstract：:We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high cor...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90010-1
更新日期：1995-01-13 00:00:00
abstract：:Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.02.038
更新日期：2010-05-25 00:00:00
abstract：:We investigated the in vitro effects of therapeutical concentrations of S 21403 (a succinic acid derivative also known as KAD 1229 and mitiglinide) on insulin and glucagon secretion during a metabolic stimulus (glucose rising from 5 to 8.33 mM) or at a stable 2.22 mM glucose using the isolated perfused rat pancreas mo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)02620-1
更新日期：2002-12-05 00:00:00
abstract：:The use-dependent effects of bunazosin on the maximal rate of rise (Vmax) of the action potential and conduction velocity were studied in isolated papillary muscles of guinea-pig. Standard microelectrode techniques were used to monitor the conduction and action potential of the muscles. In the presence of 30 microM bu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94170-3
更新日期：1990-12-04 00:00:00
abstract：:Using a batch method for incubation of hippocampal slices, we have examined the effects of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU24969) and (m-trifluoromethylphenyl)piperazine (TFMPP) on release of endogenous 5-hydroxytryotamine (5-HT). Release of 5-HT from slices was enhanced by RU24969 and TFMPP ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94111-a
更新日期：1990-11-06 00:00:00
abstract：:Nausea and vomiting are among the most frequently occurring symptoms observed by clinicians. While advances have been made in understanding both the physiological as well as the neurophysiological pathways involved in nausea and vomiting, the final common pathway(s) for emesis have yet to be defined. Regardless of the...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2013.08.047
更新日期：2014-01-05 00:00:00
abstract：:Using the radioactive microsphere technique in anaesthetized pigs, we studied the systemic and carotid haemodynamic effects of intracarotid infusions (0.3, 1, 3 and 10 micrograms/kg.min) of 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole succinate (RU 24969), a drug with high affinity for 5-HT1A and 5-HT1B reco...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90432-9
更新日期：1989-11-14 00:00:00
abstract：:Eating disorders constitute major medical health problems in the western world. Even though little is known about the mechanisms behind abnormal eating behavior, it has become clear that the central nervous system (CNS), particularly the hypothalamus, plays a significant role. The anorexic anx/anx mouse is a unique mo...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2003.08.104
更新日期：2003-11-07 00:00:00
abstract：:The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90147-3
更新日期：1981-07-17 00:00:00
abstract：:Isoflavones are compounds structurally similar to the mammalian estrogens and have received considerable attention for their preventive actions on bone loss. Here, we synthesized the novel isoflavone derivatives and examined their activities in bone cells. We found that the novel isoflavone derivatives markedly inhibi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2010.08.052
更新日期：2010-12-01 00:00:00
abstract：:BAY 41-2272 is a heme-dependent nitric oxide-independent soluble guanylate cyclase (sGC) stimulator, but its relaxant effect in vascular, respiratory and urogenital tissue is only partially dependent on sGC activation. As its mechanism of action has not been studied in the gastrointestinal tract, it was investigated i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.04.049
更新日期：2012-07-05 00:00:00
abstract：:The effects of nicotine, carbachol, hexamethonium and scopolamine were investigated on distress vocalizations (DBs) of acutely isolated domestic chicks. Nicotine attenuated, while the antimuscarinic scopolamine increased the frequency of separation-induced DVs. Furthermore, the stress attenuating effects of nicotine w...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90283-1
更新日期：1981-06-19 00:00:00
abstract：:In the guinea-pig myenteric plexus-longitudinal muscle preparation from the small intestine, the release of acetylcholine evoked by substance P and vasoactive intestinal polypeptide was examined in vitro. Both neuropeptides stimulated efflux of [3H]acetylcholine from myenteric neurons in a calcium-dependent manner. Th...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90547-9
更新日期：1986-01-21 00:00:00
abstract：:This study showed the effects of baclofen on endogenous excitatory (Glu and Asp) and non-excitatory (Tau, Gly and Ala) amino acid release. (A) Release was stimulated by K+ 30 mM in rat frontal cortex slices in vitro (evoked release in ng/g tissue per 5 min): 3739 +/- 215 (Asp), 3429 +/- 357 (Glu), 763 +/- 181 (Tau), 9...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)94813-b
更新日期：1992-11-24 00:00:00
abstract：:Alzheimer's disease, an age-related neurodegenerative disorder, is characterized clinically by a progressive loss of memory and cognitive functions. Neuropathologically, Alzheimer's disease is defined by the accumulation of extracellular amyloid protein deposited senile plaques and intracellular neurofibrillary tangle...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2006.06.026
更新日期：2006-09-01 00:00:00
abstract：:The areas S of the ventral surface of the brain stem and the immediately surrounding zone were superficially destroyed by the means of electro-coagulation, in 14 cats. This destruction produced a drop in blood pressure, which was transient in 9 and definitive in 4 animals; in one cat only the arterial pressure did not...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(75)90235-6
更新日期：1975-11-01 00:00:00
abstract：:Excessive intracellular accumulation of zinc (Zn(2+)) is neurotoxic and contributes to a number of neuropathological conditions. Here, we investigated the protective effect of 3-morpholinosydnonimine (SIN-1) against Zn(2+)-induced neuronal cell death in differentiated PC12 cells. We found that Zn(2+)-induced PC12 cell...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.12.003
更新日期：2015-02-05 00:00:00
abstract：:Multiple forms of phosphodiesterase have been reported in many tissues. Phosphodiesterase 6, a cGMP-specific phosphodiesterase, is described as a photoreceptor cell-specific phosphodiesterase. Phosphodiesterase 6 is known to play a crucial role in visual function. A novel phosphodiesterase inhibitor, GF248 (5["(propox...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00346-x
更新日期：1998-07-10 00:00:00
abstract：:We have investigated the possible mechanisms underlying the antihyperglycaemic effect of the imidazoline derivative S-22068. In vitro, in the presence of 5 mmol/l glucose, S-22068 (100 micromol/l) induced a significant and sustained increase in insulin secretion from isolated, perifused, rat islets and a marked sensit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00395-7
更新日期：1999-07-14 00:00:00
abstract：:The effect of two calmodulin inhibitors, W-7 (N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamide) and calmidazolium, on the nociceptive behavior induced by the intrathecal injection of NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-iso xazolepropionic acid) or of septide is described. Lumbar intrat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01158-8
更新日期：1997-09-17 00:00:00
abstract：:The effects of nimodipine on the amphetamine- and methamphetamine-induced decrease in central tryptophan hydroxylase activity was examined. Rats were administered 4 or 5 injections of amphetamine or methamphetamine at 6-h intervals with or without nimodipine (1 mg/kg), and killed 1 or 18 h after the last drug administ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90026-e
更新日期：1993-12-21 00:00:00
abstract：:The effect of resveratrol, an aryl hydrocarbon receptor antagonist, on the teratogenicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated. Pregnant C57BL/6J mice were orally administered resveratrol (50 mg/kg) for 6 consecutive days, from gestational day (GD) 8 to GD13, followed by an oral chall...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.05.033
更新日期：2008-09-04 00:00:00
abstract：:Rheumatoid Arthritis is a chronic autoimmune disease with a complex disease pathogenesis leading to inflammation and destruction of synovial tissue in the joint. Several molecules lead to activation of immune pathways, including autoantibodies, Toll-Like Receptor ligands and cytokines. These pathways can cooperate to ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.03.085
更新日期：2016-05-05 00:00:00
abstract：:We have previously shown that particular phenolic antidiarrheic ingredients, including 2-methoxy-4-methylphenol (2M4MP) and 2-methoxy-4-ethyphenol (2M4EP), but not 2-methoxyphenol (2MP), significantly inhibit cellular maturation and differentiation of the bone-resorbing osteoclasts with concomitant protection of the b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.03.034
更新日期：2007-07-12 00:00:00
abstract：:In the present study we investigated the in vivo pharmacological profile of the benz[e]indole cis-8-hydroxy-3-(n-propyl)],2,3a,4,5,9b-hexahydro-1H-benz[e]indole (cis-8-OH-PBZI), which has been described as a preferential dopamine D3 receptor agonist in vitro. The compound inhibited spontaneous locomotor activity in mi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01494-5
更新日期：1998-01-26 00:00:00
abstract：:To determine if an Ag(+)-induced contracture is associated with the Ca(2+)-induced Ca2+ release mechanism in the sarcoplasmic reticulum, effects of Ca(2+)-induced Ca2+ release modulators on the Ag(+)-induced contracture were studied with single fibers of frog toe skeletal muscle. The fiber treated with 1 mM caffeine c...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(95)90036-5
更新日期：1995-03-16 00:00:00
