Co-activation of µ- and δ-opioid receptors elicits tolerance to morphine-induced ventilatory depression via generation of peroxynitrite.
Respir Physiol Neurobiol
; 186(3): 255-64, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23473921
ABSTRACT
We determined whether pretreatment with (1) the µ-/δ-opioid receptor (µ-/δ-OR) antagonist, naloxone, (2) the δ1,2-OR antagonist, naltrindole, or (3) the peroxynitrite scavenger, d-penicillamine, affects the development of tolerance to the ventilatory depressant effects of morphine in rats. The injection of morphine in vehicle-pretreated rats decreased minute ventilation predominantly via decreases in tidal volume. Pretreatment with naloxone blunted the responses to morphine whereas pretreatment with naltrindole or d-penicillamine did not. A second injection of morphine, given one day later, elicited markedly smaller responses in vehicle rats whereas it elicited pronounced ventilatory depression in rats that were pretreated with naloxone, naltrindole or d-penicillamine (prior to morphine) the day before. Moreover, the ventilatory responses elicited by subsequent exposure to a hypoxic-hypercapnic challenge were markedly depressed in naloxone- or d-penicillamine-pretreated rats compared to vehicle-pretreated rats. These findings suggest that activation of µ- and δ-ORs causes tolerance to the ventilatory depressant effects of morphine at least partly via the generation of peroxynitrite.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Insuficiência Respiratória
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Receptores Opioides delta
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Receptores Opioides mu
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Ácido Peroxinitroso
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Morfina
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Entorpecentes
Limite:
Animals
Idioma:
En
Revista:
Respir Physiol Neurobiol
Ano de publicação:
2013
Tipo de documento:
Article