Respiratory function in adult mice lacking the µ-opioid receptor: role of δ-receptors

Autor:	Monique Denavit-Saubié, Arthur S. Foutz, Jean Champagnat, Eliane Boudinot, Brigitte L. Kieffer, Hans Matthes, Christelle Dubois, Marie-Pierre Morin-Surun
Rok vydání:	2001
Předmět:	Agonist medicine.medical_specialty Enkephalin medicine.drug_class General Neuroscience Pre-Bötzinger complex Biology δ-opioid receptor Endocrinology Opioid Naltrindole Internal medicine medicine Respiratory function Receptor medicine.drug
Zdroj:	European Journal of Neuroscience. 13:1703-1710
ISSN:	0953-816X
DOI:	10.1046/j.0953-816x.2001.01547.x
Popis:	Mice lacking the mu-opioid receptor (MOR) provide a unique model to determine whether opioid receptors are functionally interactive. Recent results have shown that respiratory depression produced by delta-opioid receptor agonists is suppressed in mice lacking the mu-opioid receptor. Here we investigated the involvement of mu- and delta-opioid receptors in the control of ventilation and mu/delta receptor interactions in brainstem rhythm-generating structures. Unrestrained MOR-/- and wild-type mice showed similar ventilatory patterns at rest and similar chemosensory responses to hyperoxia (100% O2), hypoxia (10% O2) or hypercapnia (5%CO2-95%O2). Blockade of delta-opioid receptors with naltrindole affected neither the ventilatory patterns nor the ventilatory responses to hypoxia in MOR-/- and wild-type mice. In-vitro, respiratory neurons were recorded in the pre-Botzinger complex of thick brainstem slices of MOR-/- and wild-type young adult mice. Respiratory frequency was not significantly different between these two groups. The delta2 receptor agonist deltorphin II (0.1-1.0 microM) decreased respiratory frequency in both groups whereas doses of the delta1 receptor agonist enkephalin[D-Pen2,5] (0.1-1.0 microM) which were ineffective in wild-type mice significantly decreased respiratory frequency in MOR-/- mice. We conclude that deletion of the mu-opioid receptor gene has no significant effect on ensuing respiratory rhythm generation, ventilatory pattern, or chemosensory control. In MOR-/- mice, the loss of respiratory-depressant effects of delta2-opioid receptor agonists previously observed in vivo does not result from a blunted response of delta receptors in brainstem rhythm-generating structures. These structures show an unaltered response to delta2-receptor agonists and an augmented response to delta1-receptor agonists.
Databáze:	OpenAIRE
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