Pharmacological identification of δ and μ opiate receptors on bulbar respiratory neurons

Morin-Surun, Marie-Pierre; Gacel, G.; Champagnat, Jean; Denavit-Saubié, Monique; Roques, Bernárd P.

doi:10.1016/0014-2999(84)90595-8

Cited by 47 publications

(19 citation statements)

References 17 publications

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“…Opioids slow discharge frequency of PBC inspiratory neurons in the neonatal brain stem preparation, and the neurons project to other areas of the VRC (35,38). In the cat, a subset, the type 2 preinspiratory neuron, exhibits a biphasic pattern of discharge that consists of a brief burst at the onset of PNA and another at the termination of the phrenic nerve inspiratory discharge (50) (Fig.…”

Section: Discussionmentioning

confidence: 99%

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Lalley¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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Lalley, Peter M. Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons. Am J Physiol Regul Integr Comp Physiol 290: R1387-R1396, 2006. First published November 10, 2005 doi:10.1152/ajpregu.00530.2005.-Opiates have effects on respiratory neurons that depress tidal volume and air exchange, reduce chest wall compliance, and slow rhythm. The most dose-sensitive opioid effect is slowing of the respiratory rhythm through mechanisms that have not been thoroughly investigated. An in vivo dose-response analysis was performed on medullary respiratory neurons of adult cats to investigate two untested hypotheses related to mechanisms of opioid-mediated rhythm slowing: 1) Opiates suppress intrinsic conductances that limit discharge duration in medullary inspiratory and expiratory neurons, and 2) opiates delay the onset and lengthen the duration of discharges postsynaptically in phase-regulating postinspiratory and late-inspiratory neurons. In anesthetized and unanesthetized decerebrate cats, a threshold dose (3 g/kg) of the -opioid receptor agonist fentanyl slowed respiratory rhythm by prolonging discharges of inspiratory and expiratory bulbospinal neurons. Additional doses (2-4 g/kg) of fentanyl also lengthened the interburst silent periods in each type of neuron and delayed the rate of membrane depolarization to firing threshold without altering synaptic drive potential amplitude, input resistance, peak action potential frequency, action potential shape, or afterhyperpolarization. Fentanyl also prolonged discharges of postinspiratory and late-inspiratory neurons in doses that slowed the rhythm of inspiratory and expiratory neurons without altering peak membrane depolarization and hyperpolarization, input resistance, or action potential properties. The temporal changes evoked in the tested neurons can explain the slowing of network respiratory rhythm, but the lack of significant, direct opioid-mediated membrane effects suggests that actions emanating from other types of upstream bulbar respiratory neurons account for rhythm slowing.fentanyl; medullary respiratory neurons; phrenic nerve activity; naloxonazine; naltrindole OPIATES ARE WELL KNOWN for their ability to depress ventilation by slowing breathing frequency and reducing tidal volume, gas exchange, upper airway patency, and chest wall compliance (3,4,36,39). They also blunt respiratory network responsiveness to hypoxia and CO 2 /acidosis (11,25,51,60).Opiate slowing of respiratory rhythm, leading to arrest of breathing after the highest doses, has been the topic of many experimental investigations (2,10,14,16,22,24,30,34,37,48,52,60). According to most recent studies, rhythm slowing seems to be principally related to depression of inspiratory interneurons in the pre-Bötzinger complex (PBC) (15, 34, 37), a region within the ventrolateral respiratory column (VRC) that seems to be critical for generation of respiratory rhythm (40, 52). However, endogenous opioid peptides are distributed throughout the bulbar respiratory ...

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Section: Discussionmentioning

confidence: 99%

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Lalley¹

2006

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Binding data have provided indications for allosteric coupling between the receptors (Rothman et al, 1993), colocalization of opioid receptors in dorsal root ganglia has been suggested by immunohistochemistry (Ji et al, 1995), and both -and ␦-receptors have been identified on bulbar respiratory neurons (Morin-Surun et al, 1984). If -/␦-receptor cross-talk occurs between populations of -and ␦-receptors co-expressed in the same neurons, we may expect that ␦-receptor transduction properties would be altered in mice lacking -receptors.…”

Section: ␦-Receptor Activity Is Slightly Reduced In Mice Lacking the mentioning

confidence: 99%

“…The activation of -, ␦-, and -opioid receptors has been reported to depress ventilation, and interactions between opioid receptors have been described on the respiratory function (Morin-Surun et al, 1984;Yeadon and Kitchen, 1989;France et al, 1994;Denavit-Saubié and Foutz, 1997). We have coupled the study of the analgesic action of deltorphin II and U50,488H with measurements of several respiratory parameters, including respiratory frequency, inspiration time, and minute volume.…”

Section: Opioid-induced Respiratory Depression In Mor-deficient Micementioning

confidence: 99%

Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor

et al. 1998

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Previous pharmacological studies have indicated the possible existence of functional interactions between -, ␦-and -opioid receptors in the CNS. We have investigated this issue using a genetic approach. Here we describe in vitro and in vivo functional activity of ␦-and -opioid receptors in mice lacking the -opioid receptor (MOR). Measurements of agonist-induced [ ] enkephalin exhibited similar potency to inhibit smooth muscle contraction in both wild-type and MOR Ϫ/Ϫ mice. ␦-Analgesia induced by deltorphin II was slightly diminished in mutant mice, when the tail flick test was used. Deltorphin II strongly reduced the respiratory frequency in wild-type mice but not in MOR Ϫ/Ϫ mice. Analgesic and respiratory responses produced by the selective -agonist U-50,488H were unchanged in MOR-deficient mice. In conclusion, the preservation of ␦-and -receptor signaling properties in mice lacking -receptors provides no evidence for opioid receptor cross-talk at the cellular level. Intact antinociceptive and respiratory responses to the -agonist further suggest that the -receptor mainly acts independently from the -receptor in vivo. Reduced ␦-analgesia and the absence of ␦-respiratory depression in MOR-deficient mice together indicate that functional interactions may take place between -receptors and central ␦-receptors in specific neuronal pathways.

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“…Furthermore, Morin-Surun et al (1984b) demonstrated that both inspiratory and expiratory neurones respond in a similar manner to the iontophoretic application of selective l-and 6-opioid agonists. However, when the same antagonists were given systemically to conscious rats Morin-Surun et al (1984a) noted that inspiratory and expiratory phases were affected differently.…”

Section: Discussionmentioning

confidence: 95%

The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats

Fone

Wilson

1986

British J Pharmacology

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1 The effects of intravenous injections of alfentanil, fentanyl, phenoperidine or morphine on respiratory and peak inspiratory air flow rate, the diaphragm electromyogram (EMG), the activity recorded extracellularly from respiratory neurones located in the ventral respiratory group and the cardiovascular system were examined in anaesthetized rats. 2 Alfentanil produced dose-dependent changes in peripheral and central respiratory parameters, which were prevented by naloxone pretreatment. Minimal effects were produced on the cardiovascular system. The bradypnoea was principally due to a prolongation of the inspiratory phase and was accompanied by a comparable decrease in the peak inspiratory air flow rate. 3 Alfentanil prolonged the discharge duration of inspiratory neurones such that it still maintained a strict phase correlation with the diaphragm EMG, but changes in firing frequency were inconsistent and negligible. The action on expiratory neuronal discharge was analogous to that on inspiratory neuronal discharge but delayed in onset. 4 Hypotension produced by morphine limited the dose used but the respiratory responses to morphine and other selected narcotic analgesics were otherwise similar to that of alfentanil, differing mainly in time-course and magnitude. From the respiratory parameters assessed, the order ofduration of effect was morphine > phenoperidine > fentanyl > alfentanil and the relative potencies were 0.1, 0.5, 2.5 and 1 respectively. 5 The selective prolongation of inspiration and the immediate action on inspiratory neurones suggests that systemically administered narcotic analgesics may alter the mechanisms within the central respiratory rhythm generator which determine the cessation of inspiration.

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Pharmacological identification of δ and μ opiate receptors on bulbar respiratory neurons

Cited by 47 publications

References 17 publications

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons

Activity of the δ-Opioid Receptor Is Partially Reduced, Whereas Activity of the κ-Receptor Is Maintained in Mice Lacking the μ-Receptor

The effects of alfentanil and selected narcotic analgesics on the rate of action potential discharge of medullary respiratory neurones in anaesthetized rats

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