Involvement of ATP-sensitive K+ channels in the peripheral antinociceptive effect induced by dipyrone

Alves, Daniela Pereira; Duarte, Igor Dimitri Gama

doi:10.1016/s0014-2999(02)01412-7

Cited by 117 publications

(69 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There have been many reports that glibenclamide specifically blocks the ATP-sensitive K + channel, with no effects on other types of K + channel such as Ca 2+ -activated K + channel and voltage-gated potassium channels (Alves & Duarte, 2002;Jesse et al, 2007;Lazaro-Ibanez et al, 2001). In the present study, we analyzed only the participation of the K + ATP channel, but we cannot disregard the possible participation of other K + channels in the antinociceptive effect of MS.…”

Section: Discussionmentioning

confidence: 97%

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

Vučković

Srebro

Vujović

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

Context: Magnesium and MK-801 (dizocilpine), antagonists of N-methyl-D-aspartate receptors, are involved in the processing of pain. Objective: This study determines whether magnesium sulfate (MS) and MK-801 affects visceral inflammatory pain and determines a possible mechanism of action. Materials and methods: Analgesic activity was assessed using the acetic acid-induced writhing test in rats. MS (1-45 mg/kg) or MK-801 (0.005-0.03 mg/kg) was administrated subcutaneously (s.c.). To assess possible mechanisms of action, we examined the effects of L-NAME (10 mg/kg, intraperitoneal), methylene blue (0.5 mg/kg, s.c.), and glibenclamide (3 mg/kg, s.c.) on the effect of MS or MK-801. Results: MS and MK-801 showed biphasic and linear dose-response pattern, respectively. MS reduces the number of writhing on the dose of 1, 5, and 15 mg/kg by 60, 50, and 78%, respectively, while it has no effects on the doses of 30 and 45 mg/kg. MK-801 (0.005-0.03 mg/kg) showed decrease in the number of writhing by 33-79%. The mean effective doses of MS and MK-801 were 6.6 (first phase) and 0.009 mg/kg, respectively. Both drugs did not impair the rotarod performance. L-NAME, methylene blue, and glybenclamide reduced the effect of MK-801 by 100, 43, and 64%, respectively, but not the effect of MS. Conclusions:The results suggest that MS and MK-801 may be useful analgesics in the management of visceral inflammatory pain, at doses that do not induce motor impairment. The modulation of NO/cGMP/K+ATP pathway plays an important role in the antinociceptive mechanism of MK-801, but does not contribute to the antinociceptive effect of MS.

show abstract

Section: Discussionmentioning

confidence: 97%

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

Vučković

Srebro

Vujović

et al. 2015

Pharmaceutical Biology

View full text Add to dashboard Cite

show abstract

“…Diclofenac can inhibit voltage-dependent Na ＋ channels in cardiac myoblasts and neurons (Lee et al, 2003;Yang and Kuo, 2005;Fei et al, 2006). It also activates neuronal K ＋ channels, such as the transient outward K ＋ currents and the ATP-sensitive potassium (KATP) channel (Tonussi and Ferreira, 1994;Asomoza-Espinosa et al, 2001;Alves and Duarte, 2002;Ortiz et al, 2002;Liu et al, 2005). However, to date, there has been no evidence of a suppressive effect of diclofenac on LCC, which is critical in working myocytes.…”

Section: Introductionmentioning

confidence: 99%

Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2+ Channels in Neonatal Rat Ventricular Cardiomyocytes

Yarishkin

Hwang

Kim

et al. 2009

Korean J Physiol Pharmacol

View full text Add to dashboard Cite

A non-steroidal anti-inflammatory drug (NSAID) has many adverse effects including cardiovascular (CV) risk. Diclofenac among the nonselective NSAIDs has the highest CV risk such as congestive heart failure, which resulted commonly from the impaired cardiac pumping due to a disrupted excitationcontraction (E-C) coupling. W e investigated the effects of diclofenac on the L-type calcium channels which are essential to the E-C coupling at the level of single ventricular myocytes isolated from neonatal rat heart, using the whole-cell voltage-clamp technique. Only diclofenac of three NSAIDs, including naproxen and ibuprofen, significantly reduced inward whole cell currents. At concentrations higher than 3 μM, diclofenac inhibited reversibly the Na ＋ current and did irreversibly the L-type Ca 2＋ channels-mediated inward current (IC50=12.89± 0.43 μM) in a dose-dependent manner. However, nifedipine, a well-known L-type channel blocker, effectively inhibited the L-type Ca 2＋ currents but not the Na ＋ current. Our finding may explain that diclofenac causes the CV risk by the inhibition of L-type Ca 2＋ channel, leading to the impairment of E-C coupling in cardiac myocytes.

show abstract

“…Early work indicated that K ATP may mediate the analgesic effects of morphine (Ocana et al 1990) or clonidine (Ocana et al 1993) since the antinociceptive effects of these agents could be reversed by pretreatment with glibenclamide, a selective K ATP antagonist. Recent studies indicate that glibenclamide can antagonize the antinociceptive effects of a variety of compounds such as nitric oxide and cyclic GMP in an assortment of animal models of nociception, such as those wherein hyperalgesia is produced by carrageenan or prostaglandin E 2 (PGE 2 ) (Rodrigues and Duarte 2000;Soares et al 2001;Alves and Duarte, 2002). Interestingly, other potassium channels blockers such as tetraethylammonium or 4-aminopyridine had no effect on the antinociception.…”

Section: Introductionmentioning

confidence: 99%

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

2007

View full text Add to dashboard Cite

Behavioral studies have shown that the hyperalgesia arising from inflammatory agents, such as prostaglandin E 2 (PGE 2 ) can be antagonized by activators of the ATP-sensitive potassium current (K ATP ). This observation raises questions as to whether this suppression results from a direct action on sensory neurons and what are the cellular mechanisms giving rise to this inhibition. We found that small to medium diameter sensory neurons isolated from the L4-6 DRGs expressed the mRNAs for Kir6.1, Kir6.2, and SUR1. In perforated-patch clamp recordings from acutely dissociated sensory neurons from the young adult rat, exposure to 300 μM diazoxide, a K ATP channel agonist, significantly hyperpolarized the resting membrane potential, reduced the number of action potentials evoked by a ramp of depolarizing current, and increased the amplitude of inward K ATP currents evoked by the voltage ramp. Similar results were obtained with the protonophore FCCP, which is known to reduce the levels of intracellular ATP and lead to the activation of K ATP . Only a subpopulation of sensory neurons was sensitive to diazoxide whereas other neurons were unaffected. Treatment with 1 μM PGE 2 significantly enhanced the excitability of these small to medium diameter capsaicin-sensitive sensory neurons; this enhancement was reversed by subsequent exposure to diazoxide in a subpopulation of neurons. Similar to diazoxide, exposure to 8-Br-cyclic GMP antagonized the PGE 2 -induced increase in excitability. The effects of 8-Br-cyclic GMP could be reversed by exposure to glibenclamide, an antagonist of K ATP channels. As with diazoxide, only a subpopulation of sensory neurons were affected by 8-Br-cyclic GMP. These results demonstrate that activation of K ATP can reverse the sensitization produced by PGE 2 and may be an important means to modulate the enhanced excitability that results from inflammatory or injury conditions.

show abstract

Involvement of ATP-sensitive K+ channels in the peripheral antinociceptive effect induced by dipyrone

Cited by 117 publications

References 23 publications

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2+ Channels in Neonatal Rat Ventricular Cardiomyocytes

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

Contact Info

Product

Resources

About

Involvement of ATP-sensitive K+ channels in the peripheral antinociceptive effect induced by dipyrone

Cited by 117 publications

References 23 publications

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K+ATP pathway

Diclofenac, a Non-steroidal Anti-inflammatory Drug, Inhibits L-type Ca2+ Channels in Neonatal Rat Ventricular Cardiomyocytes

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

Contact Info

Product

Resources

About

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway

The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K⁺ATP pathway