bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and distribution of prolactin releasing peptide (PrRP) binding sites in the rat – evidence for a novel binding site subtype in cardiac and skeletal muscle
Authors: Satoh Fumitoshi , Smith David M , Gardiner James V , Mahmoodi Mehdi , Murphy Kevin G , Ghatei Mohammad A , Bloom Stephen R 
Published: January 2005

Prolactin releasing peptide (PrRP) was recently purified from bovine hypothalamus and binds to the orphan receptor, UHR‐1. We examined the distribution and kinetics of 125I‐PrRP binding in rat tissues together with molecular characterization by chemical cross‐linking and Northern blotting.
In this study 125I‐PrRP binding showed specificity and rapid association and dissociation.
Specific binding was found in membranes from rat tissues including brain (hypothalamus, medulla oblongata and cerebellum), pituitary, heart, soleus muscle, adipose tissue, kidney, adrenal gland, testis and small intestine. In hypothalamus, pituitary, heart and soleus competition analysis indicated only one class of binding site in each tissue. Binding affinity for PrRP (IC50) and binding site density (Bmax) respectively were 5.2±0.9 nM and 674±97 fmol mg protein−1 in hypothalamus (n=5), 1.4±0.6 nM and 541±126 fmol mg protein−1 in pituitary (n=3), 6.6±0.7 nM and 628±74 fmol mg protein−1 in heart (n=4) and 9.8±0.9 nM and 677±121 fmol mg protein−1 in soleus muscle (n=4).
Analysis of 125I‐PrRP‐binding site complexes by chemical cross‐linking showed a binding site Mr of 69,000 in hypothalamus and 41,000 in heart and soleus.
Northern analysis of polyA+ RNA from hypothalamus showed a 4.2 kb band as expected for UHR‐1, but heart and soleus showed a 4.8 kb band.
Taken together these results indicate that there may be different subtypes of PrRP binding sites in rat tissues which may differ from UHR‐1.

British Journal of Pharmacology (2000) 129, 1787–1793; doi:10.1038/sj.bjp.0703266
In vitro and in vivo effects of kinin B1 and B2 receptor agonists and antagonists in inbred control and cardiomyopathic hamsters
Authors: Hallé S , Gobeil F , Ouellette J , Lambert C , Regoli D 
Published: January 2005

The aims of this study were to examine the possible alterations occurring in the effects of kinins on isolated aortae of inbred control (CHF 148) and cardiomyopathic (CHF 146) hamsters of 150–175 and 350–375 days of age.
Bradykinin (BK) and desArg9BK contracted isolated aortae (with or without endothelium) of hamsters of both strains and ages. After tissue equilibration (90 min), responses elicited by both kinin agonists were stable over the time of experiments. The patterns of isometric contractions of BK and desArg9BK were however found to be different; desArg9BK had a slower onset and a longer duration of action than BK.
Potencies (pEC50 values) of BK in all groups of hamsters were significantly increased by preincubating the tissues with captopril (10−5 M).
No differences in the pEC50 values and the Emax values for BK or desArg9BK were seen between isolated vessels from inbred control and cardiomyopathic hamsters.
The myotropic effect of BK was inhibited by the selective non peptide antagonist, FR 173657 (pIC50 7.25±0.12 at the bradykinin B2 receptor subtype (B2 receptor)). Those of desArg9BK, at the bradykinin B1 receptor subtype (B1 receptor) were abolished by either R 715 (pIC50 of 7.55±0.05; αE=0), Lys[Leu8]desArg9BK (pIC50 of 7.21±0.01; αE=0.22) or [Leu8]desArg9BK (pIC50 of 7.25±0.02; αE=0.18).
FR 173657 had no agonistic activity, exerted a non competitive type of antagonism and was poorly reversible (lasting more than 5 h) from B2 receptor. In vivo, FR 173657 (given per os at 1 and 5 mg kg−1, 1 h before the experiment) antagonized the acute hypotensive effect of BK in anaesthetized hamsters.
It is concluded that aging and/or the presence of a congenital cardiovascular disorder in hamsters are not associated with changes in the in vitro aortic responses to either BK or desArg9BK.

British Journal of Pharmacology (2000) 129, 1641–1648; doi:10.1038/sj.bjp.0703269
Exogenous cholecystokinin‐8 reduces vagal efferent nerve activity in rats through CCKA receptors
Authors: Bucinskaite Violeta , Kurosawa Mieko , Lundeberg Thomas 
Published: January 2005

It has been proposed that the vagus nerve plays a role in mediating cholecystokinin‐8 (CCK‐8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague‐Dawley rats was recorded.
Intravenous infusion of CCK‐8 (0.1–1 nmol) suppressed the efferent activity. The effect of CCK‐8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy.
Intravenous infusion of CCKA receptor antagonist L‐364,718 (1–100×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK‐8, but the CCKB receptor antagonist L‐365,260 (1–100×10−6 g) did not in the conditions of either partial or total vagotomy.
Intracisternal infusion of L‐364,718 (1×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK‐8 i.v.
Infusion of exogenous CCK‐8 did not affect the activity of supradiaphragmatic vagal afferents.
The results suggest that the effect of systemically administered CCK‐8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCKA receptors.

British Journal of Pharmacology (2000) 129, 1649–1654; doi:10.1038/sj.bjp.0703270
Characterization of the ATPase released during sympathetic nerve stimulation of the guinea‐pig isolated vas deferens
Authors: Westfall T D , Sarkar S , Ramphir N , Westfall D P , Sneddon P , Kennedy C 
Published: January 2005

The release of ATPase activity evoked by electrical field stimulation (EFS) (8 Hz, 25 s) was investigated in several tissues in which adenosine 5′‐triphosphate (ATP) acts as a neurotransmitter.
Superfusate collected during EFS of sympathetic nerves of the guinea‐pig, rat and mouse isolated vas deferens and parasympathetic nerves of the guinea‐pig isolated urinary bladder contained ATPase activity. ATP breakdown was fastest in superfusate collected from the guinea‐pig isolated vas deferens. However, EFS of the enteric nerves of the guinea‐pig isolated taenia coli did not release any detectable ATPase.
The ATPase released from the guinea‐pig isolated vas deferens metabolized ATP at similar rates at incubation temperatures of 37°C and 20°C. Lineweaver–Burke analysis of the initial rates of ATP hydrolysis gave a KM of 39 μM and a Vmax of 1039 pmol ATP metabolized min−1 ml−1 superfusate.
6‐N,N‐diethyl‐D‐β,γ‐dibromomethyleneATP (ARL 67156), pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) and pyridoxal‐5′‐phosphate (P‐5‐P) all inhibited the ATPase activity in a concentration‐dependent manner with a potency order of ARL 67156=PPADS>P‐5‐P.
In conclusion, EFS of several tissues in which ATP is a neurotransmitter causes the release of an ATPase and activity is greatest in the guinea‐pig vas deferens. The enzyme has pharmacological and kinetic characteristics that are similar to ectonucleoside triphosphate diphosphohydrolases.

British Journal of Pharmacology (2000) 129, 1684–1688; doi:10.1038/sj.bjp.0703271
Central injection of nitric oxide synthase inhibitors increases peripheral interleukin‐6 and serum amyloid A: involvement of adrenaline from adrenal medulla
Authors: Song Dong‐Keun , Im Yeong‐Bin , Jung Jun‐Sub , Yan Ji‐Jing , Huh Sung‐Oh , Suh Hong‐Won , Kim Yung‐Hi 
Published: January 2005

Accumulating evidence suggests that plasma levels of interleukin‐6 (IL‐6), a major cytokine stimulating the synthesis of acute phase proteins, are intimately regulated by the central nervous system (CNS).
In the present study, effects of intracerebroventricular (i.c.v) injection of NG‐nitro‐L‐arginine methyl ester (L‐NAME) or 7‐nitroindazole, nitric oxide synthase (NOS) inhibitors, on plasma IL‐6 levels and peripheral IL‐6 mRNA expression were examined in mice.
L‐NAME (0.1–2 μg per mouse i.c.v.) and 7‐nitroindazole (0.2–2 μg per mouse i.c.v.) induced a dose‐dependent increase in plasma IL‐6 levels and a subsequent increase in circulating serum amyloid A, a liver acute‐phase protein. In contrast, an intraperitoneal (i.p.) injection of L‐NAME up to the dose of 25 μg per mouse had no effect.
Pretreatment with yohimbine (α2‐adrenergic antagonist; 1 mg kg−1 i.p.), or ICI‐118,551 (β2‐adrenergic antagonist; 2 mg kg−1 i.p.), but not with prazosin (α1‐adrenergic antagonist; 1 mg kg−1 i.p.), nor betaxolol (β1‐adrenergic antagonist; 2 mg kg−1 i.p.), significantly inhibited the central L‐NAME‐induced plasma IL‐6 levels.
I.c.v. (50 μg per mouse) or i.p. (100 mg kg−1) pretreatment with 6‐hydroxydopamine had no effect on central L‐NAME‐induced plasma IL‐6 levels. However, intrathecal (i.t.) pretreatment with 6‐hydroxydopamine (20 μg per mouse) markedly inhibited central L‐NAME‐induced plasma IL‐6 levels. Both yohimbine (1.5 μg per mouse i.t.) and ICI‐118,551 (1.5 μg per mouse i.t.) were effective in inhibition of central L‐NAME‐induced plasma IL‐6 levels.
There was an elevation of base‐line plasma IL‐6 levels in adrenalectomized animals. The adrenalectomy‐enhanced levels were not further increased by central L‐NAME.
L‐NAME (2 μg per mouse i.c.v.) induced an increase in IL‐6 mRNA expression in liver, spleen, and lymph node.
These results suggest that NOS activity in the brain tonically down‐regulates peripheral IL‐6 by inhibiting adrenaline release from the adrenal medulla.

British Journal of Pharmacology (2000) 130, 41–48; doi:10.1038/sj.bjp.0703273
Peroxynitrite‐mediated release of arachidonic acid from PC12 cells
Authors: Guidarelli Andrea , Palomba Letizia , Cantoni Orazio 
Published: January 2005

A short term exposure of PC12 cells to a concentration of tert‐butylhydroperoxide (tB‐OOH) causing peroxynitrite‐dependent DNA damage and cytotoxiticity promoted a release of arachidonic acid (AA) that was sensitive to phospholipase A2 (PLA2) inhibitors and insensitive to phospholipase C or diacylglycerol lipase inhibitors. The extent of AA release was also mitigated by nitric oxide synthase (NOS) inhibitors and peroxynitrite scavengers. Low levels (10 μM) of authentic peroxynitrite restored the release of AA mediated by tB‐OOH in NOS‐inhibited cells whereas concentrations of peroxynitrite of 20 μM, or higher, effectively stimulated a PLA2 inhibitor‐sensitive release of AA also in the absence of additional treatments. These results are consistent with the possibility that endogenous as well as exogenous peroxynitrite promotes activation of PLA2.British Journal of Pharmacology (2000) 129, 1539–1542; doi:10.1038/sj.bjp.0703275
Neurokinin B‐ and specific tachykinin NK3 receptor agonists‐induced airway hyperresponsiveness in the guinea‐pig
Authors: Daoui Samira , Naline Emmanuel , Lagente Vincent , Emonds‐Alt Xavier , Advenier Charles 
Published: January 2005

The aim of this study was to determine whether neurokinin B (NKB) or specific agonists of tachykinin NK3 receptors, [MePhe7]NKB and senktide, were able to induce airway hyperresponsiveness in guinea‐pigs. The effects of these compounds were compared to those of substance P (SP), neurokinin A (NKA) and the preferential tachykinin NK1 ([Sar9, Met(02)11]SP) or NK2 ([βAla8]NKA (4‐10)) receptor agonists.
In guinea‐pigs pretreated with phosphoramidon (10−4 M aerosol for 10 min) and salbutamol (8.7×10−3 M for 10 min), all tachykinins administrated by aerosol (3×10−7 to 10−4 M) induced airway hyperresponsiveness 24 h later, displayed by an exaggerated response to the bronchoconstrictor effect of acetylcholine (i.v.). The rank order of potency was: [βAla8]NKA (4‐10)>NKA=NKB=senktide=[MePhe7]NKB=[Sar9,Met(02)11]SP>SP.
Airway hyperresponsiveness induced by [MePhe7]NKB was prevented by the tachykinin NK3 (SR 142801) and NK2 (SR 48968) receptor antagonists.
Bronchoconstriction induced by tachykinins administered by aerosol was also determined. SP, NKA, NKB and the tachykinin NK1 and NK2 receptor agonist induced bronchoconstriction. The rank order of potency was: NKA=[βAla8]NKA (4‐10)>NKB=SP=[Sar9,Met(02)11]SP. Under similar conditions, and for concentrations which induce airway hyperresponsiveness, senktide and [MePhe7]NKB failed to induce bronchoconstriction.
It is concluded that tachykinin NK3‐receptor stimulation can induce airway hyperresponsiveness and that this effect is not related to the ability of tachykinins to induce bronchoconstriction.

British Journal of Pharmacology (2000) 130, 49–56; doi:10.1038/sj.bjp.0703278
Inhibitory mechanism of tranilast in human coronary artery smooth muscle cells proliferation, due to blockade of PDGF‐BB‐receptors
Authors: Watanabe Shinji , Matsuda Akihisa , Suzuki Yasuhiro , Kondo Kazunao , Ikeda Yasuhiko , Hashimoto Hisakuni , Umemura Kazuo 
Published: January 2005

We have previously reported that tranilast, an anti‐allergic drug, prevented the experimental intimal thickening in the rat and mouse femoral arteries and its effect may be exerted through the inhibition of vascular smooth muscle cell proliferation. However, its inhibitory mechanism has yet to be understood.
In this study, we investigated the inhibitory effect of tranilast on platelet‐derived growth factor BB‐homodimer (PDGF‐BB) mediated signal transduction pathways in cultured human coronary artery smooth muscle cells (CASMCs).
Growth responses to PDGF‐BB were measured by [3H]‐thymidine incorporation or cell counting. Activation of DNA synthesis and augmentation of cell proliferation stimulated by PDGF‐BB in quiescent cultures of CASMCs were inhibited by tranilast in a concentration‐dependent manner.
Western blot analysis of lysates from CASMCs with an anti‐activated mitogen‐activated protein (MAP) kinase antibody revealed that tranilast (10–300 μM) inhibited MAP kinase activation by PDGF‐BB in a concentration‐dependent manner. Tranilast also reduced PDGF‐BB‐stimulated tyrosine phosphorylation of a 180 kDa band, corresponding in mass to the PDGF β‐receptor, as shown by immunoblots using an anti‐phosphotyrosine antibody.
Receptor‐binding study with [125I]‐PDGF‐BB on CASMCs showed that tranilast (10–1000 μM) inhibited the specific binding of PDGF‐BB to cell surface receptors in a concentration‐dependent manner. Scatchard analysis revealed that pretreatment with 300 μM tranilast decreased the maximum binding capacity (Bmax) from 27.6 to 18.0 fmol 106 cells−1 without affecting binding affinity (Kd∼0.15 nM), indicating a non‐competitive inhibition of the receptor binding.
These results suggest that the suppression of human CASMC growth by tranilast might be at least partly due to blockade of PDGF‐BB‐receptor binding.

British Journal of Pharmacology (2000) 130, 307–314; doi:10.1038/sj.bjp.0703285
The role of nitric oxide in the responses of the ovine digital artery to vasoactive agents and modification of these responses by endotoxin and cytokines
Authors: Pawson P , Reid J , Nolan A M 
Published: January 2005

Laminitis, an important cause of lameness in domestic ungulates, occurs as a result of altered digital perfusion. Endotoxin and cytokines may mediate the vascular derangements observed through alterations in nitric oxide production. In this study, the vascular responses of the isolated ovine digital artery were examined and the influence of endotoxin and cytokines investigated.Neither removal of the endothelium nor incubation with NG‐nitro‐L‐arginine methyl ester (L‐NAME, 300 μM) altered the response to phenylephrine (PE, 1 nMto 300 μM). Indomethacin (10 μM) decreased PE log EC50from −6.22±0.08 to −6.55±0.07. Acetylcholine (1 nMto 1 mM) and bradykinin (BK, 100 pMto 3 μM) induced endothelium‐dependent relaxation. Bradykinin‐induced relaxation was reduced byL‐NAME, Emaxfalling from −61.7±7.4 to −34.0±2.1%. Addition of indomethacin further reduced BK Emaxto −9.6±2.8%. Sodium nitroprusside (1 nMto 300 μM) produced endothelium‐independent relaxation that was unaffected byL‐NAME or indomethacin.Following a 6 h incubation with endotoxin (3 μg ml−1), arterial responses to PE and BK did not differ from polymyxin B‐treated controls (10 μg ml−1). Arteries incubated for 6 h with interferon‐γ (IFN‐γ, 10 ng ml−1) and tumour necrosis factor‐α (TNF‐α, 5 ng ml−1) exhibited greater relaxation to BK (Emax−50.0±5.1%) than polymyxin B‐treated controls (Emax−33.1±4.0%), but did not differ in their response to PE.Prolonged incubation (16 h) with endotoxin (3 μg ml−1) did not alter the response to PE, however incubation with IFN‐γ (10 ng ml−1), TNF‐α (5 ng ml−1) and interleukin‐1β (20 ng ml−1) for 16 h increased PE log EC50from −6.44±0.09 to −6.10±0.11.Nitric oxide is an important mediator of endothelium‐dependent relaxation in ovine digital arteries but does not modulate PE‐induced vasoconstriction. Incubation with cytokines decreased the sensitivity of digital arteries to PE.British Journal of Pharmacology(2000)130, 109–117; doi:10.1038/sj.bjp.0703286
In vivo effects of the 5‐HT6 antagonist SB‐271046 on striatal and frontal cortex extracellular concentrations of noradrenaline, dopamine, 5‐HT, glutamate and aspartate
Authors: Dawson L A , Nguyen H Q , Li P 
Published: January 2005

Although the 5‐HT6 receptor subtype was identified some 5 years ago, very little is known about its function within the brain. Here we demonstrate, for the first time, the neurochemical effects of a selective 5‐HT6 receptor ligand. Using in vivo microdialysis in the freely moving rat, we evaluated the effects of the selective 5‐HT6 receptor antagonist SB‐271046 by simultaneous measurement of 5‐hydroxytryptamine (5‐HT), dopamine (DA), noradrenaline (NA), glutamate and aspartate from the striatum and frontal cortex. SB‐271046 did not alter basal levels of 5‐HT, DA and NA in either brain region. Similarly, there was no change basal levels of either of the excitatory amino acids within the striatum. In contrast, administration of SB‐271046 (10 mg kg−1 s.c.) produced a significant (P<0.05), tetrodotoxin‐dependent, increase in extracellular levels of both glutamate and aspartate within the frontal cortex, reaching maximum values of 375.4±82.3 and 215.3±62.1% of preinjection values, respectively.British Journal of Pharmacology (2000) 130, 23–26; doi:10.1038/sj.bjp.0703288
Rapid desensitization of the TRH receptor and persistent desensitization of its constitutively active mutant
Authors: Zaltsman Ilona , Grimberg Hagit , Lupu‐Meiri Monica , Lifschitz Ilana , Oron Yoram 
Published: January 2005

We studied rapid desensitization of the thyrotropin‐releasing hormone receptor (TRH‐R) or the m1‐muscarinic receptor (m1‐R) to a short challenge of threshold TRH concentration and persistent desensitization due to constitutive activity of a mutant TRH‐R.
Xenopus oocytes expressing TRH‐Rs and/or m1‐Rs were challenged for 15 s with threshold concentrations of TRH ([TRH]) and then immediately with supraoptimal [TRH] or acetylcholine ([ACh]). The threshold challenge caused desensitization of 50–57% of responses to subsequent supraoptimal stimulation with TRH or ACh.
The homologous desensitization was reversible within 60 s after removal of the agonist.
The protein kinase C (PKC) inhibitor, chelerythrine, inhibited the control responses by 30–40%, without affecting the desensitized responses. Chelerythrine or the phosphatase inhibitor, okadaic acid, had little effect on the kinetics of resensitization, indicating limited involvement of PKC.
In oocytes coexpressing wild type TRH‐Rs or m1‐Rs with a constitutively active TRH‐R mutant (C335Stop TRH‐R), a persistent desensitization (33–57%) of the responses to TRH or ACh was observed. Additionally, there was a complete loss of the rapid desensitization induced by threshold [TRH].
Chlorodiazepoxide (CDE), a competitive binding antagonist of TRH‐Rs and an inverse agonist of C335Stop TRH‐Rs, abolished the persistent desensitization induced by C335Stop TRH‐Rs and enabled the rapid desensitization, conferring the wild type phenotype on C335Stop TRH‐Rs. Chelerythrine had qualitatively the same effect as CDE.
In conclusion, unlike the rapid desensitization, the persistent desensitization caused by the constitutively active C335Stop TRH‐Rs is largely mediated by PKC. It abrogates, however, the rapid desensitization, suggesting a common mechanistic step(s).

British Journal of Pharmacology (2000) 130, 315–320; doi:10.1038/sj.bjp.0703291
Characterization of the binding of two novel glycine site antagonists to cloned NMDA receptors: evidence for two pharmacological classes of antagonists
Authors: Chopra Bela , Chazot Paul L , Stephenson F Anne 
Published: January 2005

The potency of two novel glycine site antagonists, GV150,526A and GV196,771A, was assessed by their ability to inhibit the binding of [3H]‐MDL105,519 to cell homogenates prepared from mammalian cells transfected with either NR1‐1a, NR1‐2a, NR1‐1a/NR2A, NR1‐1a/NR2B, NR1‐1a/NR2C or NR1‐1a/NR2D NMDA receptor clones.
The inhibition constants (Kis) for GV150,526A displacement of [3H]‐MDL105,519 binding to either NR1‐1a or NR1‐2a expressed alone were not significantly different and were best fit by a one‐site binding model. GV150,526A inhibition to NR1‐1a/NR2 combinations was best fit by a two‐site model with the NR1‐1a/NR2C having an approximate 2–4 fold lower affinity compared to other NR1‐1a/NR2 receptors.
The Kis for GV196,771A displacement of [3H]‐MDL105,519 binding to NR1‐1a, NR1‐2a and all NR1‐1a/NR2 combinations was best fit by a two‐site binding model. There was no significant difference between the Kis for the binding to NR1‐1a and NR1‐2a; NR1‐1a/NR2A receptors had an approximate 4 fold lower affinity for GV196,771A compared to other NR1‐1a/NR2 combinations.
The Kis for both GV150,526A and GV196,771A for the inhibition of [3H]‐MDL105,519 binding to membranes prepared from adult rat forebrain were determined and compared to the values obtained for binding to cloned NMDA receptors.
The Kis for a series of glycine site ligands with diverse chemical structures were also determined for the inhibition of [3H]‐MDL105,519 binding to NR1‐1a/NR2A receptors. L689,560 displayed similar binding characteristics to GV150,526A.
It is suggested that glycine site antagonists may be divided into two classes based on their ability to distinguish between NR1 and NR1/NR2 receptors with respect to binding curve characteristics.

British Journal of Pharmacology (2000) 130, 65–72; doi:10.1038/sj.bjp.0703298