bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of c‐fos expression in the heart after morphine but not U‐50,488H withdrawal
Authors: González‐Cuello Ana , Milanés M Victoria , Castells M Teresa , Laorden M Luisa 
Published: February 2003

In the present work we have studied in the heart the expression of Fos, the protein product of the c‐fos proto‐oncogene and the adaptive changes in noradrenergic neurons after naloxone or nor‐binaltorphimine (nor‐BNI) administration to morphine or U‐50,488H pretreated rats.
Male rats were implanted with placebo (naïve) or morphine (tolerant/dependent) pellets for 7 days. On day 8 rats received saline s.c., naloxone (5 mg kg−1 s.c.) or nor‐BNI (5 mg kg−1 i.p.). Other groups of rats were rendered tolerant/dependent on U‐50,488H by injecting the drug twice daily (15 mg kg−1 i.p.) for 4 days. Control animals received saline. On day 5 the animals were injected with vehicle i.p. or nor‐BNI (5 mg kg−1 i.p.).
Using immunohistochemical staining of Fos, present results indicate that morphine withdrawal induced marked Fos immunoreactivity (Fos‐IR) within the cardiomyocyte nuclei. Moreover, Western blots analysis revealed a peak expression of c‐fos in right and left ventricle after naloxone induced withdrawal in parallel with an increase in noradrenaline (NA) turnover.
However, after nor‐BNI administration to rats chronically treated with U‐50,488H, we found a decrease in the NA turnover. In addition, the administration of nor‐BNI to rats chronically treated with U‐50,488H or morphine did not induce modifications in the Fos‐IR, in the heart.
These results demonstrated that morphine withdrawal induces the expression of Fos protein, as well as an enhancement of noradrenergic activity in the heart. In contrast to morphine U‐50,488 withdrawal produces no changes in Fos‐IR in parallel with a decrease in NA turnover, indicating that the kappa–opioid receptors are not involved in the molecular adaptive mechanisms responsible for the development of opioid dependence in the heart.

British Journal of Pharmacology (2003) 138, 626–633. doi:10.1038/sj.bjp.0705093
CC chemokines induce P‐selectin‐dependent neutrophil rolling and recruitment in vivo: intermediary role of mast cells
Authors: Wan Ming Xiu , Wang Yusheng , Liu Qing , Schramm Rene , Thorlacius Henrik 
Published: February 2003

Based on in vitro chemotaxis experiments, it is widely held that CC chemokines, such as macrophage inflammatory protein‐1α (MIP‐1α) and macrophage chemotactic protein‐1 (MCP‐1) mainly support lymphocyte trafficking.
The objective of the present study was to examine the role of MIP‐1α and MCP‐1 in neutrophil recruitment in vivo by use of intravital microscopy of the mouse cremaster microcirculation.
MIP‐1α and MCP‐1 caused a dose‐dependent increase in leukocyte rolling, adhesion and recruitment. Indeed, neutrophils comprised more than 85% of the leukocyte response to MIP‐1α and MCP‐1. An anti‐P‐selectin antibody reduced MIP‐1α and MCP‐1‐provoked leukocyte rolling by more than 94%. Concomitantly, firm adhesion and extravasation of neutrophils in response to MIP‐1α and MCP‐1 challenge were significantly decreased by more than 78 and 84%, respectively. In contrast, an anti‐E‐selectin antibody had no influence on CC chemokine‐induced neutrophil recruitment.
Flow cytometric analysis revealed that MIP‐1α and MCP‐1 had no effect on P‐selectin expression on endothelial cells, suggesting that neutrophil recruitment elicited by CC chemokines in vivo is not mediated via a direct effect on the endothelium but rather via an indirect effect involving activation of an intermediary tissue cell. Indeed, it was found that MIP‐1α‐induced neutrophil accumulation was significantly decreased by 58% in mast cell‐deficient mice.
These findings demonstrate that CC chemokines trigger P‐selectin‐dependent rolling and tissue recruitment of neutrophils via tissue mast cells in vivo and suggest that CC chemokines may also be important targets in neutrophil‐mediated tissue damage in multicellular organs.

British Journal of Pharmacology (2003) 138, 698–706. doi:10.1038/sj.bjp.0705094
Thrombin‐induced conversion of fibrinogen to fibrin results in rapid platelet trapping which is not dependent on platelet activation or GPIb
Authors: Jarvis Gavin E , Atkinson Ben T , Frampton Jon , Watson Steve P 
Published: February 2003

Activation of human platelets by thrombin is mediated by the proteolytic cleavage of two G‐protein coupled protease‐activated receptors, PAR‐1 and PAR‐4. However, thrombin also binds specifically to the platelet surface glycoprotein GPIb. It has been claimed that thrombin can induce aggregation of platelets via a novel GPIb‐mediated pathway, which is independent of PAR activation and fibrinogen binding to αIIbβ3 integrin, but dependent upon polymerizing fibrin and the generation of intracellular signals.
In the presence of both fibrinogen and the αIIbβ3 receptor antagonist lotrafiban, thrombin induced a biphasic platelet aggregation response. The initial primary response was small but consistent and associated with the release of platelet granules. The delayed secondary response was more substantial and was abolished by the fibrin polymerization blocking peptide GPRP.
Cleavage of the extracellular portion of GPIb by mocarhagin partially inhibited thrombin‐induced αIIbβ3‐dependent aggregation and release, but had no effect on the secondary fibrin‐dependent response.
Fixing of the platelets abolished αIIbβ3‐dependent aggregation and release of adenine nucleotides, whereas the fibrin‐dependent response remained, indicating that platelet activation and intracellular signalling are not necessary for this secondary ‘aggregation’.
In conclusion, the secondary fibrin‐dependent ‘aggregation’ response observed in the presence of fibrinogen and lotrafiban is a platelet trapping phenomenon dependent primarily on the conversion of soluble fibrinogen to polymerizing fibrin by thrombin.

British Journal of Pharmacology (2003) 138, 574–583. doi:10.1038/sj.bjp.0705095 doi:0705095a/sj.bjp.0704832
A possible mechanism for improvement by a cognition‐enhancer nefiracetam of spatial memory function and cAMP‐mediated signal transduction system in sustained cerebral ischaemia in rats
Authors: Takeo Satoshi , Niimura Makiko , Miyake‐Takagi Keiko , Nagakura Akira , Fukatsu Tomoko , Ando Tsuyoshi , Takagi Norio , Tanonaka Kouichi , Hara Junko 
Published: February 2003

Accumulated evidence indicates that the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP‐responsive element binding protein (CREB) signal transduction system may be linked to learning and memory function.
The effects of nefiracetam, which has been developed as a cognition enhancer, on spatial memory function and the AC/cAMP/PKA/CREB signal transduction system in rats with sustained cerebral ischaemia were examined.
Microsphere embolism (ME)‐induced sustained cerebral ischaemia was produced by injection of 700 microspheres (48 μm in diameter) into the right hemisphere of rats. Daily oral administration of nefiracetam (10 mg kg−1 day−1) was started from 15 h after the operation.
The delayed treatment with nefiracetam attenuated the ME‐induced prolongation of the escape latency in the water maze task that was examined on day 7 to 9 after ME, but it did not reduce the infarct size.
ME decreased Ca2+/calmodulin (CaM)‐stimulated AC (AC‐I) activity, cAMP content, cytosolic PKA Cβ level, nuclear PKA Cα and Cβ levels, and reduced the phosphorylation and DNA‐binding activity of CREB in the nucleus in the right parietal cortex and hippocampus on day 3 after ME. The ME‐induced changes in these variables did not occur by the delayed treatment with nefiracetam.
These results suggest that nefiracetam preserved cognitive function, or prevented cognitive dysfunction, after sustained cerebral ischaemia and that the effect is, in part, attributable to the prevention of the ischaemia‐induced impairment of the AC/cAMP/PKA/CREB signal transduction pathway.

British Journal of Pharmacology (2003) 138, 642–654. doi:10.1038/sj.bjp.0705096
Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex
Authors: Lorez Matthias , Humbel Urs , Pflimlin Marie‐Claire , Kew James N C 
Published: February 2003

Group III metabotropic glutamate receptors (mGluRs) of the subtype 4a are localized within presynaptic active zones of cerebellar parallel fibre (PF)‐Purkinje cell (PC) synapses. In order to investigate the conditions necessary for group III mGluR autoreceptor‐activation by synaptically released glutamate, we characterized the effects of selective agonists and antagonists on excitatory postsynaptic currents (EPSCs) evoked by several distinct PF stimulation patterns.
The group III mGluR‐selective agonist L‐AP4 depressed evoked EPSCs at PF‐PC synapses in rat brain slices with an EC50 of 2.4 μM and maximum inhibition of 80%. This L‐AP4‐induced depression was antagonized by the group III mGluR‐selective antagonist MSOP with an estimated equilibrium dissaciation constant of 12.5 μM.
Paired‐pulse or four‐pulse PF stimulations did not activate presynaptic group III mGluRs as revealed by the lack of effect of 1 mM MSOP on relative test EPSC amplitudes with latencies of 250–500 ms. The potentiation of a test EPSC evoked 200–500 ms after a short tetanic burst (100 Hz for 60 ms), was also unchanged in the presence of MSOP.
Endogenous autoreceptor‐activation was revealed only during prolonged stimulation trains (10 Hz for 4.4 s), where, in the presence of 1 mM MSOP, the EPSC amplitudes were enhanced by 15%.
These observations support an autoreceptor function of group III mGluRs and a role in short‐term synaptic plasticity at PF synapses. However, the low to moderate activation levels observed, despite the close spatial relation with glutamate release sites, suggests that additional mechanisms regulate receptor activation.

British Journal of Pharmacology (2003) 138, 614–625. doi:10.1038/sj.bjp.0705099
The CB1 receptor antagonist SR141716A selectively increases monoaminergic neurotransmission in the medial prefrontal cortex: implications for therapeutic actions
Authors: Tzavara Eleni T , Davis Richard J , Perry Kenneth W , Li Xia , Salhoff Craig , Bymaster Frank P , Witkin Jeffrey M , Nomikos George G 
Published: February 2003

In order to explore potential therapeutic implications of cannabinoid antagonists, the effects of the prototypical cannabinoid antagonist SR141716A on monoamine efflux from the medial prefrontal cortex and the nucleus accumbens of the rat were investigated by in vivo microdialysis.
SR141716A moderately increased serotonin efflux and concentrations of its metabolite 5‐HIAA, both in the medial prefrontal cortex and the nucleus accumbens, and increased norepinephrine, dopamine and their metabolites in the medial prefrontal cortex. In contrast, it had no effect on norepinephrine, dopamine and their metabolites in the nucleus accumbens.
At the same doses, SR141716A increased acetylcholine efflux in the medial prefrontal cortex, in agreement with previous studies; contrary to the effects in cortex, SR141716A had no effect on acetylcholine efflux in the nucleus accumbens.
The efficacy of SR141716A in the psychostimulant‐induced hyperlocomotion and the forced swimming paradigms was also explored in mice. SR141716A attenuated phenylcyclidine‐ and d‐amphetamine‐induced hyperlocomotion, without affecting locomotor activity when administered alone, and decreased immobility in the forced swimming test.
These results suggest that the cortical selectivity in the release of catecholamines, dopamine in particular, induced by the cannabinoid antagonist SR141716A, its procholinergic properties, together with its mild stimulatory effects on serotonin and norepinephrine efflux make similar compounds unique candidates for the treatment of psychosis, affective and cognitive disorders.

British Journal of Pharmacology (2003) 138, 544–553. doi:10.1038/sj.bjp.0705100
G protein‐coupled receptor kinase 6 (GRK6) selectively regulates endogenous secretin receptor responsiveness in NG108‐15 cells
Authors: Ghadessy Roxana S , Willets Jonathon M , Kelly Eamonn 
Published: February 2003

To determine the role of G protein‐coupled receptor kinases (GRKs) in the regulation of endogenous secretin receptor responsiveness, we have transiently overexpressed both wild‐type (WT) and dominant negative mutant (DNM) GRKs in NG108‐15 mouse neuroblastoma×rat glioma hybrid cells and investigated the effects of this on agonist‐stimulated adenylyl cyclase activity.Overexpression of WT GRK6 selectively inhibited secretin‐stimulated cyclic AMP accumulation (fold stimulation of cyclic AMP above basal following 15 min incubation with 100 nMsecretin was 12.1±2.0 and 6.2± 0.8 in control and WT GRK overexpressing cells, respectively) without affecting cyclic AMP responses mediated by the adenosine A2receptor agonist 5′‐(N‐ethylcarboxamido) adenosine (NECA) or the prostanoid‐IP receptor agonist iloprost, or the direct activator of adenylyl cyclase, forskolin. On the other hand DNM GRK6 (Lys215Arg) overexpression produced the opposite effect – a selective increase in the secretin‐stimulated cyclic AMP response was observed in cells overexpressing DNM GRK6 compared to plasmid‐transfected cells (fold stimulation of cyclic AMP above basal following 15 min incubation with 100 nMsecretin was 12.6±2.7 and 29.6±5.6 for control and DNM GRK6‐overexpressing cells, respectively).Overexpression of WT GRK5 likewise inhibited the secretin‐stimulated cyclic AMP response, however, this effect was not as selective as with GRK6, since adenosine A2receptor responsiveness was also suppressed by GRK5 overexpression. Unlike DNM GRK6, overexpression of DNM GRK5 failed to modulate secretin or A2adenosine receptor signalling suggesting that endogenous GRK5 is unlikely to regulate desensitization of these receptors in NG108‐15 cells.Overexpression of WT GRK2 did not affect secretin‐stimulated cyclic AMP accumulation. Instead, GRK2 overexpression selectively inhibited A2adenosine receptor responsiveness, confirming our previous findings.Together these results suggest a selective role of endogenous GRK6 in regulating secretin receptor responsiveness in NG108‐15 cells. In addition, these data indicate that GRKs exert a surprising degree of selectivity in the regulation of natively expressed GPCR responses.British Journal of Pharmacology(2003)138, 660–670. doi:10.1038/sj.bjp.0705101
Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats
Authors: Ibuki Takae , Marsala Martin , Masuyama Takashi , Yaksh Tony L 
Published: February 2003

We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance.
Rats received lumbar intrathecal (IT) infusion of morphine (IT‐M: 20 nmol μl−1 h−1) or saline (IT‐S: 1 μl h−1) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP‐N: 0.6 mg kg−1) or saline (IP‐S: 3 ml kg−1) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured.
Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine+IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine+i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups.
For the IT‐M+IP‐N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3‐day infusion interval. No change in basal resting release was noted for any other treatment.
Evoked release (after i.p. naloxone) in IT‐M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups.
The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection.
The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance.

British Journal of Pharmacology (2003) 138, 689–697. doi:10.1038/sj.bjp.0705102
Branching Out: A Molecular Fingerprint of Endothelial Differentiation into Tube‐Like Structures Generated by Affymetrix Oligonucleotide Arrays
Authors: GERRITSEN MARY E. , SORIANO ROBERT , YANG SUYA , ZLOT CONSTANCE , INGLE GLADYS , TOY KAREN , WILLIAMS P. MICKEY 
Published: February 2003

ABSTRACTThe process of endothelial differentiation into a network of tube‐like structures with patent lumens requires an integrated program of gene expression. To identify genes upregulated in endothelial cells during the process of tube formation, RNA was prepared from several different time points (0, 4, 8, 24, 40, and 48 hours) and from three different experimental models of human endothelial tube formation: in collagen gels and fibrin gels driven by the combination of PMA (80), bFGF (40 ng/ml) and bFGF (40 ng/ml) or in collagen gels driven by the combination of HGF (40 ng/ml) and VEGF (40 ng/ml). Gene expression was evaluated using Affymetrix® Gene Chip® oligonucleotide arrays. Over 1000 common genes were upregulated greater than twofold over baseline at one or more time points in the three different models. In the present study, we discuss the identified genes that could be assigned to major functional classes: apoptosis, cytoskeleton, proteases, matrix, and matrix turnover, pumps and transporters, membrane lipid turnover, and junctional molecules or adhesion proteins.
The effect of infant colic on maternal self‐perceptions and mother‐‐infant attachment
Authors: Stifter C A , Bono M A 
Published: February 2003

SummaryMothers of infants who developed colic were compared with mothers of non‐colic infants on their perceptions of parenting self‐efficacy, and separation anxiety as well as their attachment relationship with their infants. Colic was identified prospectively through telephone contacts with mothers. Questionnaires on self‐efficacy and separation anxiety were completed when infants were 5 months of age. At 18 months of age mothers and infants (colic and non‐colic) participated in a laboratory situation to measure attachment. Results revealed that mothers of colic infants reported feeling less competent as mothers. In addition, while mothers of colicky infants tended to have more separation anxiety than mothers of non‐colic infants, they felt that these separations did not have a negative effect on their child. Finally, no differences were revealed for attachment classifications between colic and non‐colic infants at 18 months.
Links between maternal care and persistent infant crying in the early months
Authors: St James‐Roberts I , Conroy S , Wilsher K 
Published: February 2003

SummaryA community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups — of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers— were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below‐optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings’ implications for professionals are discussed.
Relationships between infant crying, birth complications, and maternal variables
Authors: Keller H , Lohaus A , VÎlker S , Cappenberg M , Chasiotis A 
Published: February 2003

SummaryThe aim of the study is to identify factors influencing infants’ crying behaviour (total crying duration, length of crying bouts, and frequency of crying). The searching for variables explaining inter‐individual differences requires a sufficient stability of the cry parameters at least over short time intervals. Thus, a second aim is to assess the intra‐individual stability of the crying behaviour in an age range from 3 to 12 months. Sixty‐two mother–child dyads participated in the study. The results show substantial stabilities of the crying behaviour of infants between 3 and 12 months of age. This is related to the amount of crying as well as to the pattern of crying shown by the children over a 24 h interval. The typical cry pattern is characterized by peaks at 12.00 h and early in the evening, although there are large individual differences between the children with regard to cry durations at each hour of the day. Regarding the cry durations at 3 months of age, birth complications and the perceived emotional atmosphere in the mothers’ family of origin are the major contributing factors.
A two‐fold difference in the age‐adjusted prevalences of Parkinson’s disease between the island of Als and the Faroe Islands
Authors: Wermuth L. , von Weitzel‐Mudersbach P. , Jeune B. 
Published: February 2003

With the aim of comparing the previously found high prevalence of idiopathic Parkinson’s disease (PD) in the Faroe Islands with the prevalence of PD in an area of Denmark, we used the same case‐finding methods for case ascertainment and the same strict criteria to diagnose PD on the island of Als. During the last year before the prevalence date (1 January 1998), we found in various registries from pharmacies, hospital, private neurologist and general practioners 121 patients with suspected Parkinsonism out of 56 839 inhabitants on the island of Als. After exclusion of those who had other diseases, a total of 79 patients were left for further examinations. Among these we found 58 with PD. The overall prevalence of PD was estimated to be 102.0 and the age‐adjusted prevalence to be 98.3 per 100 000 persons compared with 187.6 and 209.0 in the Faroe Islands. Compared with the previous results from the Faroe Islands (prevalence date 1 July 1995) we found an even lower mean age at onset of PD symptoms and at onset of treatment, a lower proportion of definite PD and a lower average dose of levodopa. We therefore conclude that the two‐fold higher prevalence in the Faroe Islands than on the island of Als was not due to an early diagnosis and a higher ascertainment of cases with mild PD, which was suggested as being one possible explanation for our previous finding of a high prevalence of PD in the Faroe Islands.