Pharmacological characterisation of novel kinin B2 receptor ligands

2002 ◽  
Vol 80 (4) ◽  
pp. 281-286 ◽  
Author(s):  
V Camarda ◽  
A Rizzi ◽  
G Calò ◽  
K Wirth ◽  
D Regoli
Keyword(s):  
Key Words ◽  
Receptor Subtypes ◽  
Receptor Ligands ◽  
Agonist Peptide ◽  
Key Words Bradykinin ◽  
Potency Order

Peptide and nonpeptide compounds have been shown to interact specifically with B2 receptors of three different species, namely human, rabbit, and pig. Peptide agonists and nonpeptide antagonists show marked differences in potencies and suggest the existence of B2 receptor subtypes. This conclusion is based on data obtained with the modified agonist peptide LF 150943 whose potency (pEC50 9.4) is at least 100-fold higher in rabbit than in humans (7.4) and pig (6.7). The same conclusion can be drawn from data obtained with antagonists that are more potent in humans (LF 160687, pA2 9.2) than in rabbit (8.7) and pig (8.2) or with antagonists (S 1567) that show the opposite potency order, being much weaker in humans (pA2 6.9) than in rabbit (7.6) and pig (9.4). Two other compounds (FR 173657 and FR 172357) show similar pharmacological spectra as S 1567 and differ from LF 160687.Key words: bradykinin, B2 receptor ligands, bioassay, isolated vessels.

Stereochemistry of serotonin receptor ligands from crystallographic data. Crystal structures of NAN-190.HBr, 1-phenylbiguanide, MDL 72222 and mianserin.HCl and selectivity criteria towards 5-HT1, 5-HT2 and 5-HT3 receptor subtypes

1996 ◽  
Vol 52 (3) ◽  
pp. 509-518 ◽  
Author(s):  
A. Dalpiaz ◽  
V. Ferretti ◽  
P. Gilli ◽  
V. Bertolasi
Keyword(s):  
Structural Analysis ◽  
Serotonin Receptor ◽  
Molecular Structures ◽  
Receptor Subtypes ◽  
Receptor Ligands ◽  
Endogenous Ligand ◽  
Constant Length ◽  
Mdl 72222 ◽  
Crystal And Molecular Structures ◽  
Pharmacophoric Feature

The crystal and molecular structures of the following serotoninergic drugs have been determined: (1) 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide hemihydrate (NAN-190.HBr), C23H28N3O3 +.Br−.1/2H2O, Mr = 483.42, monoclinic, C2/c, a = 21.916 (4), b = 15.207 (2), c = 14.052 (2) Å, β = 101.56 (1)°, V = 4588 (1) Å3, Z = 8, Dx = 1.40 Mg m−3, λ(Mo Kα) = 0.71069 Å, μ = 1.823 mm−1, F(000) = 2008, T = 295 K, R = 0.035 for 2617 observed reflections; (2) N-phenylimidocarbonimidic diamide (1-phenylbiguanide), C8H11N5, Mr = 177.21, monoclinic, P21/c, a = 9.781 (2), b = 35.040 (5), c = 11.000 (2) Å, β = 97.72 (1)°, V = 3736 (1) Å3, Z = 16, Dx = 1.26 Mg m−3, λ(Mo Kα) = 0.71069 Å, μ= 0.084 mm−1, F(000) = 1504, T = 295 K, R = 0.070 for 3407 observed reflections; (3) 8-methyl-8-azabicyclo[3.2.1.]oct-3-yl 3,5-dichlorobenzoate (MDL 72222), C15H17C12NO2, Mr = 314.21, triclinic, P{\bar 1}, a = 8.480 (3), b = 9.840 (3), c = 10.15 (4) Å, α = 90.04 (3), β = 111.77 (3), γ = 105.07 (3)°, V = 755.6 (5) Å3, Z = 2, Dx = 1.38 Mg m−3, λ(Mo Kα) = 0.71069 Å, μ = 0.430 mm−1, F(000) = 328, T = 295 K, R = 0.070 for 1685 observed reflections; (4) 1,2,3,4,10,14b-hexahydro-2-methyldibenzo[cf]pyrizino[1,2-a]azepine hydrochloride (mianserin.HCl), C18H21N2 +.Cl−, Mr = 300.83, monoclinic, P21/a, a = 9.014 (2), b = 14.917 (2), c = 12.412 (2) Å, β = 108.84 (1)°, V = 1579.5 (5) Å3, Z = 4, Dx = 1.26 Mg m−3, λ(Mo Kα) = 0.71069 Å, μ = 0.237 mm−1, F(000) = 640, T = 295 K, R = 0.063 for 1493 observed reflections. A systematic structural analysis of the present compounds and others known to interact with the 5-HT1, 5-HT2 and 5-HT3 receptors allows to identify their similarities with the endogenous ligand serotonin (5-HT) and the stereochemical differences which determine selectivity for the various receptor subtypes. The pharmacophoric feature for 5-HT receptor binding is identified in a constant-length vector linking an aromatic ring with a protonated nitrogen, while specific affinities for receptorial subtypes and the nature of the effect appear to be modulated by the dimensions of the substituents at nitrogen.

scholarly journals Effect of the Gintonin-Enriched Fraction on Glucagon-Like-Protein-1 Release

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6298
Author(s):  
Rami Lee ◽  
Sun-Hye Choi ◽  
Han-Sung Cho ◽  
Hongik Hwang ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Western Blotting ◽  
Receptor Activation ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Dependent Manner ◽  
Receptor Ligands ◽  
Lpa Receptor ◽  
Beneficial Effects

Ginseng-derived gintonin reportedly contains functional lysophosphatidic acids (LPAs) as LPA receptor ligands. The effect of the gintonin-enriched fraction (GEF) on in vitro and in vivo glucagon-like protein-1 (GLP-1) secretion, which is known to stimulate insulin secretion, via LPA receptor(s) remains unclear. Accordingly, we examined the effects of GEF on GLP-1 secretion using human enteroendocrine NCI-H716 cells. The expression of several of LPA receptor subtypes in NCI-H716 cells using qPCR and Western blotting was examined. LPA receptor subtype expression was in the following order: LPA6 > LPA2 > LPA4 > LPA5 > LPA1 (qPCR), and LPA6 > LPA4 > LPA2 > LPA1 > LPA3 > LPA5 (Western blotting). GEF-stimulated GLP-1 secretion occurred in a dose- and time-dependent manner, which was suppressed by cAMP-Rp, a cAMP antagonist, but not by U73122, a phospholipase C inhibitor. Furthermore, silencing the human LPA6 receptor attenuated GEF-mediated GLP-1 secretion. In mice, low-dose GEF (50 mg/kg, peroral) increased serum GLP-1 levels; this effect was not blocked by Ki16425 co-treatment. Our findings indicate that GEF-induced GLP-1 secretion could be achieved via LPA6 receptor activation through the cAMP pathway. Hence, GEF-induced GLP secretion via LPA6 receptor regulation might be responsible for its beneficial effects on human endocrine physiology.

Modulation of the components of the rat dark-adapted electroretinogram by the three subtypes of GABA receptors

2003 ◽  
Vol 20 (5) ◽  
pp. 535-542 ◽  
Author(s):  
ANNA MÖLLER ◽  
THOR EYSTEINSSON
Keyword(s):  
Gaba Receptors ◽  
Plexiform Layer ◽  
Amacrine Cells ◽  
Electric Activity ◽  
Oscillatory Potentials ◽  
Receptor Subtypes ◽  
Inner Plexiform Layer ◽  
Receptor Ligands ◽  
Cellular Origin ◽  
Stimulation Of

The separate components of the dark-adapted electroretinogram (ERG) are believed to reflect the electric activity of neurones in both the inner and the outer layers of the retina, although their precise origin still remains unclear. The purpose of this study was to examine whether selective blockage or stimulation of the different subtypes of GABA receptors might help further elucidate the cellular origin of the components of the dark-adapted ERG. The rat retina is of interest since the localization and physiology of GABA receptors in that retina have been examined in great detail. GABA agonists and antagonists, known to affect the responses of neurons in the inner plexiform layer, were injected into the vitreous of one eye while ERG responses evoked by flashes of white light were recorded. GABA and the GABAa agonist isoguvacine completely removed the oscillatory potentials (OPs) and reduced the amplitude of the a- and b-waves. TPMPA, a GABAc antagonist, reduced the a- and b-waves but had no significant effect on the OPs. Baclofen, a GABAb agonist, reduced the amplitude of the a- and b-waves, without having any effects on the amplitude of the OPs. The GABAb antagonist CGP35348 increased the amplitudes of the a- and b-wave without having an effect on the amplitudes of the OPs. The GABAb receptor ligands had significant and opposite effect on the latency of the OPs. These results indicate that retinal neurons, presumably a subpopulation of amacrine cells, that have GABAb receptors are not the source of the OPs of the ERG, although they may modulate these wavelets in some manner, while contributing to the generation of the dark-adapted a- and b-waves. OPs are modified by stimulation of GABAa receptors, and the a- and b-waves by stimulation of all GABA receptor subtypes.

Neuropeptide Y Receptor Subtypes and Putative Receptor Ligands

1993 ◽  
pp. 175-186 ◽  
Author(s):  
THOMAS HEDNER ◽  
XIANG-YING SUN ◽  
LARS EDVINSSON
Keyword(s):  
Neuropeptide Y ◽  
Receptor Subtypes ◽  
Receptor Ligands ◽  
Putative Receptor ◽  
Neuropeptide Y Receptor

scholarly journals Histamine receptors in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Paul Chazot ◽  
Marlon Cowart ◽  
Hiroyuki Fukui ◽  
C. Robin Ganellin ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Acid Reflux ◽  
Histamine Receptor ◽  
Histamine Receptors ◽  
Vestibular Neuritis ◽  
Receptor Subtypes ◽  
Endogenous Ligand ◽  
H3 Receptor ◽  
Ligand Bias ◽  
H1 Antagonists ◽  
Potency Order

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [80, 173]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [80]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [173]. Some agonists at the human H3 receptor display significant ligand bias [182]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. adriforant; Phase IIa) [173] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [216, 8].

scholarly journals Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels

2011 ◽  
Vol 300 (2) ◽  
pp. C328-C337 ◽  
Author(s):  
Molly Johannessen ◽  
Dominique Fontanilla ◽  
Timur Mavlyutov ◽  
Arnold E. Ruoho ◽  
Meyer B. Jackson
Keyword(s):  
Receptor Subtypes ◽  
Receptor Ligands ◽  
Patch Clamp Recording ◽  
Membrane Action ◽  
Channel Modulation ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Wide Range ◽  
Liver Membranes ◽  
Antagonist Action

σ-Receptors are integral membrane proteins that have been implicated in a number of biological functions, many of which involve the modulation of ion channels. A wide range of synthetic ligands activate σ-receptors, but endogenous σ-receptor ligands have proven elusive. One endogenous ligand, dimethyltryptamine (DMT), has been shown to act as a σ-receptor agonist. Progesterone and other steroids bind σ-receptors, but the functional consequences of these interactions are unclear. Here we investigated progesterone binding to σ1- and σ2-receptors and evaluated its effect on σ-receptor-mediated modulation of voltage-gated Na+ channels. Progesterone binds both σ-receptor subtypes in liver membranes with comparable affinities and blocks photolabeling of both subtypes in human embryonic kidney 293 cells that stably express the human cardiac Na+ channel Nav1.5. Patch-clamp recording in this cell line tested Na+ current modulation by the σ-receptor ligands ditolylguanidine, PB28, (+)SKF10047, and DMT. Progesterone inhibited the action of these ligands to varying degrees, and some of these actions were reduced by σ1-receptor knockdown with small interfering RNA. Progesterone inhibition of channel modulation by drugs was consistent with stronger antagonism of σ2-receptors. By contrast, progesterone inhibition of channel modulation by DMT was consistent with stronger antagonism of σ1-receptors. Progesterone binding to σ-receptors blocks σ-receptor-mediated modulation of a voltage-gated ion channel, and this novel membrane action of progesterone may be relevant to changes in brain and cardiovascular function during endocrine transitions.

scholarly journals Histamine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Paul Chazot ◽  
Marlon Cowart ◽  
Hiroyuki Fukui ◽  
C. Robin Ganellin ◽  
Ralf Gutzmer ◽  
...  
Keyword(s):  
Acid Reflux ◽  
Histamine Receptor ◽  
Histamine Receptors ◽  
Vestibular Neuritis ◽  
Receptor Subtypes ◽  
Endogenous Ligand ◽  
H3 Receptor ◽  
Ligand Bias ◽  
H1 Antagonists ◽  
Potency Order

Histamine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Histamine Receptors [75, 163]) are activated by the endogenous ligand histamine. Marked species differences exist between histamine receptor orthologues [75]. The human and rat H3 receptor genes are subject to significant splice variance [12]. The potency order of histamine at histamine receptor subtypes is H3 = H4 > H2 > H1 [163]. Some agonists at the human H3 receptor display significant ligand bias [171]. Antagonists of all 4 histamine receptors have clinical uses: H1 antagonists for allergies (e.g. cetirizine), H2 antagonists for acid-reflux diseases (e.g. ranitidine), H3 antagonists for narcolepsy (e.g. pitolisant/WAKIX; Registered) and H4 antagonists for atopic dermatitis (e.g. ZPL-3893787; Phase IIa) [163] and vestibular neuritis (AUV) (SENS-111 (Seliforant, previously UR-63325), entered and completed vestibular neuritis (AUV) Phase IIa efficacy and safety trials, respectively) [205, 8].

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