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Zalozenia technologiczne otrzymywania preparatow z bielma ostropestu plamistego do stosowania jako dodatki przeciwutleniajace

100%

Szczucinska A., Kurzepa K., Kleczkowska P., Lipkowski A. W.

Rośliny Oleiste - Oilseed Crops

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2006

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tom 27

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nr 2

357-366

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Neurotensin NTS1 receptors mediate the cardio-respiratory effects of [Ile 9]PK20, a novel chimeric peptide

100%

Kaczynska K., Szereda-Przestaszewska M., Kleczkowska P., Lipkowski A. W.

Acta Neurobiologiae Experimentalis

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2013

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tom 73

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nr 1

Opioids with their large potency in pain relieve have certain undesirable effects like tolerance, dependence and respiratory depression. This is the reason for permanent efforts to create new analgesic compounds devoid of the adverse side effects. PK20 is a novel hybrid of opioidneurotensin peptides synthetized from the C-terminal hexapeptide of neurotensin and endomorphine-2 pharmacophore. This chimeric compound shows clear central and peripheral antinociceptive activity in experimental animals, however nothing is known about the influence of PK20 on respiratory and cardiovascular parameters. The present study was designed to determine the cardiorespiratory effects exerted by an intravenous injection of [Ile9]PK20, analog of PK20 with substitution of tert-leucine by isoleucine9. We also attempted to evaluate whether the effects of the hybrid are mediated by the peripheral neural pathway like vagus nerve. Finally, the contribution of NTS1 neurotensin and opioid receptors in the [Ile9]PK20 cardiorespiratory pattern was tested. Anaesthetized, spontaneously breathing rats were used. Tidal volume was measured at tracheostomy. The timing components of the breathing pattern, arterial blood pressure and heart rate were recorded. Intravenous injection of [Ile9]PK20 at a dose of 100 μg/kg in the intact rats provoked an increase in tidal volume preceded by a prompt shortlived decrease. Immediately after the end of injection brief acceleration of the respiratory rhythm, was ensued by the slowing down of breathing. Changes in respiration were concomitant with a bi-phasic response of the blood pressure: immediate increase was followed by prolonged hypotension. Bilateral midcervical vagotomy eliminated both: tidal volume and respiratory rate responses. Blockade of NTS1 receptors with an intravenous dose of 500 μg/kg of SR 142948, significantly lessened post-[Ile9]PK20 cardiorespiratory effects. Naloxone hydrochloride – antagonist of opioid receptors – failed to block [Ile9]PK20-evoked responses. This study depicts that [Ile9]PK20 acting through neurotensin NTS1 receptors augments the tidal component of the breathing pattern through the vagal pathway. This latter mediates also the respiratory timing response to the drug. Blood pressure effects evoked by an intravenous injection of [Ile9]PK20 occur besides the vagal pathway and might result from activation of the central and peripheral vascular NTS1 receptors. In summary the respiratory effects appeared not to be profound. However, considerable and extended hypotension evoked by [Ile9]PK20 sets the main disadvantage of an analgesic compound.

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Novel, highly antinociceptive hybrid compound in acute pain

76%

Kleczkowska P., Kosson P., Van der Eynde I., Tsuda Y., Tourwe D., Lipkowski A. W.

Acta Neurobiologiae Experimentalis

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2011

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tom 71

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nr 1

The clinical treatment of various types of pain relies upon opioid analgesic, however most of them produce, in addition to the analgesic effect, several side effects such as development of dependence and addiction as well as sedation, dysphoria, and constipation. One of the solutions to these problems are chimeric compounds in which opioid pharmacophore is hybridized with other type of synergically active antinociceptor. Neurotensin-induced antinociception is not mediated through the opioid system. Therefore, hybridizing neurotensin with opioid element may result in a potent synergic antinociceptor. The opioid-neurotensin hybride analogue PK20, in which opioid and neurotensin pharmacophores partially overlapped, expresses high antinociceptive tail-flick effects after central as well as peripheral applications. The antinociceptive effects likely are result of synergistic/additive interaction of hybridized opioid and neurotensin pharmacophores.

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Role of the blood - brain barrier in differential response to opioid peptides and morphine in mouse lines divergently bred for high and low swim stress - induced analgesia

64%

Kosson A., Krizbai I., Lesniak A., Beresewicz M., Sacharczuk M., Kosson P., Nagyoszi P., Wilhelm I., Kleczkowska P., Lipkowski A. W.

Acta Neurobiologiae Experimentalis

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2014

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tom 74

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nr 1

Over 20 years ago, the Sadowski group separated two mouse lines, one with high (HA) and the other with low (LA) sensitivity to swim stress-induced analgesia (SSIA). Recently, we proposed that increased leakage of the blood-brain barrier (BBB) in the HA line created the difference in the response to SSIA. To search for further evidence for this hypothesis, differences in the levels of the BBB proteins occludin and claudin-5 were analysed. In addition, we sought to evaluate practical differences in BBB permeability by examining the antinociceptive levels in HA and LA mouse lines after i.v. administration of peptides that have limited access to the CNS. Western blot was used to analyse the differences between occludin and claudin-5. To evaluate the functional differences between the BBB of HA and LA mice, the antinociception levels of endomorphin I, biphalin and AA2016 (peptides with limited BBB permeabilities) in the tail flick test were examined. The expression levels of occludin and claudin-5 in the HA mouse line were lower than in the LA and control mice. Central antinociception of the opioid peptides were significantly higher in the HA line than in the LA and control lines. Our data support the hypothesis that BBB leakage is responsible for the differences between the HA and LA mouse lines. Although SSIA confirmed BBB differences between both lines, it is not limited to the opioid system and could be a useful model for studying the role of the BBB in molecular communications between the periphery and CNS.

5

Determination of the anti-inflammatory properties and analgesic activity of the AA3052 chimeric peptide against CFA-induced inflammatory pain

51%

Kowalczyk A., Kleczkowska P., Konop M., Kasarello K., Czuwara J., Pekala M., Sosnowski P., Sacharczuk M., Cudnoch-Jedrzejewska A., Rudnicka L., Bujalska-Zadrozny M.

Animal Science Papers and Reports

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2018

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tom 36

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nr 2

Ograniczanie wyników

Zalozenia technologiczne otrzymywania preparatow z bielma ostropestu plamistego do stosowania jako dodatki przeciwutleniajace

Neurotensin NTS1 receptors mediate the cardio-respiratory effects of [Ile 9]PK20, a novel chimeric peptide

Novel, highly antinociceptive hybrid compound in acute pain

Role of the blood - brain barrier in differential response to opioid peptides and morphine in mouse lines divergently bred for high and low swim stress - induced analgesia

Determination of the anti-inflammatory properties and analgesic activity of the AA3052 chimeric peptide against CFA-induced inflammatory pain