102,251 research outputs found
Portishead Point, Church and Mouth of the Avon
No full text'PORTISHEAD POINT, CHURCH AND MOUTH OF THE AVON. On Stone by J. Horner from a drawing by T. L. Rowbotham, Day & Haghe Lithrs to the King, Gate St. Linc: Inn Fds. Published by G. Davey Bookseller, Broad St. Bristol.
Effects of nociceptin and endomorphin 1 on the electrically stimulated human vas deferens
No full textAims To examine the effects of nociceptin (NC) and endomorphin 1 (EM1) on
electrical ®eld stimulation (EFS)-induced contractions of the human vas deferens
(hVD).
Methods Concentration-response curves to NC and EM1 were constructed in the
absence and in presence of peptidase inhibitors (PI). In some experiments a NC
receptor antagonist, [Phe1y(CH2-NH)Gly2]NC(1±13)NH2 [F/G], 10 mM) or naloxone
(1 mM) were included.
Results All data are mean(95%CI). In the presence of PI, NC inhibited twitches
(Emax=67(44,90)%; pEC50=7.28(6.95,7.61)). NC inhibition was sensitive to [F/G].
EM1 also inhibited twitches both in the absence (Emax=82(73,91)% pEC50=7.07
(6.92,7.22)) and presence (Emax=83(76,90)%; pEC50=7.00(6.91, 7.09)) of PI. EM1
inhibition was sensitive to naloxone.
Conclusions These data suggest that hVD express NC and opioid receptors that
inhibit neurogenic contractions
Assessment of the activity of a novel nociceptin/orphanin FQ analogue at recombinant human nociceptin/orphanin FQ receptors expressed in Chinese hamster ovary cells
No full textThe neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the nociceptin receptor (NOP). In an attempt to identify
high potency NOP agonists for use in the brain we have compared the activity of a novel N/OFQ analogue [Phe1C(CH2-O)Gly2]N/OFQ(1-
13)NH2 ([F/G-O]) with the existing [Phe1C(CH2-NH)Gly2]N/OFQ(1-13)NH2 ([F/G]). Both peptides are modified between the first two Nterminal
amino acids and are further compared with the agonist template N/OFQ(1-13)NH2 in [3H]N/OFQ binding, GTPg[35S] binding and
cAMP inhibition studies using Chinese hamster ovary cells expressing the recombinant human NOP. All peptides displaced [3H]N/OFQ,
stimulated GTPg[35S] binding and inhibited cAMP formation. In [3H]N/OFQ binding and GTPg[35S] binding the rank order affinity and
potency was N/OFQ(1-13)NH2 . [F/G-O] . [F/G]. In GTPg[35S] binding [F/G] was a clear partial agonist with intrinsic activity (Emax
stimulation factor, mean ^ SEM, n 1⁄4 4) of 7.75 ^ 1.02 compared with N/OFQ(1-13)NH2 of 11.13 ^ 1.76. The efficacy of [F/G-O]
(10.17 ^ 1.88) approached that of the full agonist N/OFQ(1-13)NH2. Downstream, at the level of cAMP formation, all peptides were full
agonists with the following rank order potency: N/OFQ(1-13)NH2 . [F/G-O] 1⁄4 [F/G]. The enhanced potency and intrinsic activity of the
novel [F/G-O] modification makes this an interesting peptide for further in vivo analysis
Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys(10,14)]N/OFQ(1-14)NH2 and c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH2
No full textIn this study we describe the activity of two
cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys10,14]N/
OFQ(1–14)NH2 (c[Cys10,14]) and its [Nphe1] derivative
c[Nphe1,Cys10,14]N/OFQ(1–14)NH2 (c[Nphe1,Cys10,14]) in
native rat and mouse and recombinant human N/OFQ receptors
(NOP). Cyclisation may protect the peptide from
metabolic degradation.
In competition binding studies of rat, mouse and human
NOP the following rank order pKi was obtained: N/OFQ(1–
13)NH2(reference agonist)>N/OFQ=c[Cys10,14]>>c[Nphe1Cys10,14].
In GTPγ35S studies of Chinese hamster ovary cells expressing
human NOP (CHOhNOP) c[Cys10,14] (pEC50 8.29)
and N/OFQ(1–13)NH2 (pEC50 8.57) were full agonists
whilst c[Nphe1Cys10,14] alone was inactive. Following 30 min
pre-incubation c[Nphe1Cys10,14] competitively antagonised
the effects of N/OFQ(1–13)NH2 with a pA2 and slope factor
of 6.92 and 1.01 respectively. In cAMP assays c[Cys10,14]
(pEC50 9.29, Emax 102% inhibition of the forskolin stimulated
response), N/OFQ(1–13)NH2 (pEC50 10.16, Emax
103% inhibition) and c[Nphe1Cys10,14] (~80% inhibition
at 10 μM) displayed agonist activity. In the mouse vas
deferens c[Cys10,14] (pEC50 6.82, Emax 89% inhibition of
electrically evoked contractions) and N/OFQ(1–13)NH2
(pEC50 7.47, Emax 93% inhibition) were full agonists whilst
c[Nphe1Cys10,14] alone was inactive. c[Nphe1Cys10,14]
(10 μM) competitively antagonised the effects of N/OFQ(1–
13)NH2 with a pKB of 5.66. In a crude attempt to assess
metabolic stability, c[Cys10,14] was incubated with rat brain
membranes and then the supernatant assayed for remaining
peptide. Following 60 min incubation 64% of the 1 nM
added peptide was metabolised (compared with 54% for
N/OFQ-NH2).
In summary, we report that c[Cys10,14] is a full agonist
with a small reduction in potency but no improvement in
stability whilst c[Nphe1Cys10,14] displays tissue (antagonist
in the vas deferens) and assay (antagonist in the GTPγ35S
assay and agonist in cAMP assay) dependent activity
(1999). Comparison of the effects of [Phe1psi(CH2-NH)Gly2]Nociceptin (1-13)NH2 in rat brain, rat vas deferens and CHO cells expressing recombinant human nociceptin receptors
No full text1 Nociceptin(NC) is the endogenous ligand for the opioid receptor like-1 receptor (NC-receptor).
[Phe1C(CH2-NH)Gly2]Nociceptin(1-13)NH2 ([F/G]NC(1-13)NH2) has been reported to antagonize
NC actions in peripheral guinea-pig and mouse tissues. In this study, we investigated the e ects of a
range of NC C-terminal truncated fragments and [F/G]NC(1-13)NH2 on NC receptor binding,
glutamate release from rat cerebrocortical slices (rCX), inhibition of cyclic AMP accumulation in
CHO cells expressing the NC receptor (CHONCR) and electrically evoked contractions of the rat vas
deferens (rVD).
2 In radioligand binding assays, a range of ligands inhibited [125I]-Tyr14-NC binding in membranes
from rCX and CHONCR cells. As the peptide was truncated there was a general decline in pKi.
[F/G]NC(1-13)NH2 was as potent as NC(1-13)NH2.
3 The order of potency for NC fragments to inhibit cyclic AMP accumulation in whole CHONCR
cells was NCNH25NC=NC(1-13)NH24NC(1-12)NH244NC(1-11)NH2. [F/G]NC(1-13)NH2 was
a full agonist with a pEC50 value of 8.65.
4 NCNH2 and [F/G]NC(1-13)NH2 both inhibited K+ evoked glutamate release from rCX with
pEC50 and maximum inhibition of 8.16, 48.5+4.9% and 7.39, 58.9+6.8% respectively.
5 In rVD NC inhibited electrically evoked contractions with a pEC50 of 6.63. Although
[F/G]NC(1-13)NH2, displayed a small (instrinsic activity a=0.19) but consistent residual agonist
activity, it acted as a competitive antagonist (pA2 6.76) in the rVD.
6 The di erences between [F/G]NC(1-13)NH2 action on central and peripheral NC signalling could
be explained if [F/G]NC(1-13)NH2 was a partial agonist with high strength of coupling in the CNS
and low in the periphery. An alternative explanation could be the existence of central and peripheral
receptor isoforms
The effect of guanethidine and local anaesthetics on the electrically stimulated mouse vas deferens
No full textComplex regional pain syndrome is often treated with the sympatholytic guanethidine and a local anesthetic in a Bier's block. The efficacy of this treatment has been questioned. Because local anesthetics inhibit the norepinephrine uptake transporter, we hypothesized that this variable efficacy results from the local inhibiting the uptake of guanethidine. In this study, we tested this hypothesis by using a sympathetically innervated mouse vas deferens preparation. Organ bath-mounted mouse vasa deferentia were electrically stimulated in the absence and presence of guanethidine, prilocaine, procaine, and cocaine in various combinations. Prilocaine (1 mM) induced an immediate inhibition of twitch response (maximum 100% after 2 min) that fully reversed after washing. Guanethidine (3 microM) also inhibited twitching by 95% +/- 3% in 15 min, but this effect was only partially reversed after 1 h of washing (33% +/- 12% of control). When prilocaine and guanethidine were added in combination, a reversal of 80% +/- 13% (at 1 h) was observed. Procaine (300 micro M) produced a transient increase (152% +/- 14%) in response. When co-incubated with guanethidine (3 microM), the twitch was reduced to 24% +/- 4% of control and was reversed to 77% +/- 7% after 1 h. Cocaine (30 microM) inhibited the twitch response to 53% +/- 8%, which was fully reversed by 1 h of washing. When co-incubated with guanethidine, the response was reduced to 39% +/- 6% of control and was reversed to 86% +/- 10% after 1 h. In all cases, the reversal produced by the combination was significantly more intense (P < 0.05) than that produced by guanethidine alone. Local anesthetics reduce the sympatholytic actions of guanethidine, and this may explain the variable efficacy of guanethidine in the treatment of complex regional pain syndrome
Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung
No full textDieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio
Dispelling the Myths Behind First-author Citation Counts
No full textWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pharmacological characterization of the bifunctional opioid ligand H-Dmt-Tic-Gly-NH-Bzl (UFP-505)
No full textBACKGROUND: While producing good-quality analgesia, μ-opioid (MOP) receptor activation produces a number of side-effects including tolerance. Simultaneous blockade of δ-opioid (DOP) receptors has been shown to reduce tolerance to morphine. Here, we characterize a prototype bifunctional opioid H-Dmt-Tic-Gly-NH-Bzl (UFP-505).
METHODS: We measured receptor binding affinity in Chinese hamster ovary (CHO) cells expressing recombinant human MOP, DOP, k-opioid (KOP), nociceptin/orphanin (NOP) receptors. For activation, we measured the binding of GTPγ(35)S to membranes from CHO(hMOP), CHO(hDOP), rat cerebrocortex, and rat spinal cord. In addition, we assessed 'end organ' responses in the guinea pig ileum and mouse vas deferens.
RESULTS: UFP-505 bound to CHO(hMOP) and CHO(hDOP) with (binding affinity) pK(i) values of 7.79 and 9.82, respectively. There was a weak interaction at KOP and NOP (pK(i) 6.29 and 5.86). At CHO(hMOP), UFP-505 stimulated GTPγ(35)S binding with potency (pEC(50)) of 6.37 and in CHO(hDOP) reversed the effects of a DOP agonist with affinity (pK(b)) of 9.81 (in agreement with pK(i) at DOP). UFP-505 also stimulated GTPγ(35)S binding in rat cerebrocortex and spinal cord with pEC(50) values of 6.11-6.53. In the guinea pig ileum (MOP-rich preparation), UFP-505 inhibited contractility with pEC(50) of 7.50 and in the vas deferens (DOP-rich preparation) reversed the effects of a DOP agonist with an affinity (pA(2)) of 9.15.
CONCLUSIONS: We have shown in a range of preparations and assays that UFP-505 behaves as a potent MOP agonist and DOP antagonist; a MOP/DOP bifunctional opioid. Further studies in dual expression systems and whole animals with this prototype are warranted
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