μ‐opioid receptors are present in functionally identified sympathoexcitatory neurons in the rat rostral ventrolateral medulla

Aicher, Sue A.; Schreihofer, Ann M.; Kraus, James A.; Sharma, Sarita; Milner, Teresa A.; Guyenet, Patrice G.

doi:10.1002/cne.1123

Cited by 40 publications

(28 citation statements)

References 49 publications

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“…The cardiovascular sympathoinhibitory, depressor, and bradycardic responses to fentanyl after premamillary transection appear to be mediated by -opioid receptors in the vicinity of the RVLM, since they were eliminated by microinjections of naloxone into the RVLM. -Opioid receptors have been localized in the RVLM (3,21,35), and sympathoinhibitory responses accompanying their stimulation in the RVLM have been described (21,36,49). From our data, it appears that in the intact animal, the cardiovascular sympathoexcitatory effects elicited from fentanyl binding to -opioid receptors in a site rostral to the brain stem predominate over the cardiovascular sympathoinhibitory effects elicited from fentanyl stimulation of -opioid receptors in the RVLM.…”

Section: Discussionmentioning

confidence: 58%

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Cao¹,

Morrison²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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Mu-opioid receptor activation increases body temperature and affects cardiovascular function. In the present study, fentanyl was administered intravenously [100 mug/kg (300 nmol/kg) iv] and intracerebroventricularly [3.4 mug (10 nmol) in 10 microl icv] in urethane-chloralose-anesthetized, artificially ventilated rats. Increases in brown adipose tissue (BAT) sympathetic nerve activity (SNA) (peak, +326% of control), BAT temperature (peak, +0.8 degrees C), renal SNA (peak, +146% of control), and heart rate (HR; peak, +32 beats/min) produced by intravenous fentanyl were abolished by premamillary transection of the neuraxis but were mimicked by intracerebroventricular administration of fentanyl, which also increased arterial pressure (AP; peak, +12 mmHg). Pretreatment with the opioid antagonist naloxone (100 nmol in 10 microl icv) eliminated the intracerebroventricular fentanyl-evoked responses. Microinjection of glycine (0.5 M, 60 nl) to inhibit local neurons in the rostral raphe pallidus (RPa) selectively reversed the intracerebroventricular fentanyl-evoked increases in BAT SNA and HR, while the fentanyl-evoked excitation in RSNA, the pressor responses, and the tachycardic responses were reversed by inhibition of neurons in the rostral ventrolateral medulla (RVLM). Prior inhibition of neurons in the dorsomedial hypothalamus eliminated the intracerebroventricular fentanyl-evoked increases in BAT SNA, BAT temperature, and HR, but not those in RSNA or AP. These results indicate that activation of central mu-opioid receptors with fentanyl can elicit BAT thermogenesis and cardiovascular stimulation through excitation of the sympathetic outflows to BAT, kidney, and heart. Activation of neurons in the rostral RPa and RVLM are essential for the increases in BAT thermogenesis and renal sympathoexcitation, respectively, induced by activation of central mu-opioid receptors. BAT thermogenesis could contribute to fentanyl-evoked hyperthermia, particularly in infants where BAT plays a significant role in thermoregulation.

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Section: Discussionmentioning

confidence: 58%

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Cao¹,

Morrison²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…However, in contrast to delta receptor agonism in the RVLM, mu-opioid agonism causes an attenuation of the sympathetic baroreceptor reflex with no effect on the somatosympathetic reflex (Miyawaki et al 2002). Mu-opioid receptors are found both pre-and postsynaptically on neurons in the RVLM with a very marked post-synaptic preponderance (Aicher et al 2001). Such a morphological arrangement would permit mu agonists to occlude baroreceptor inputs arising from inhibitory neurons in the caudal ventrolateral medulla (figure 1b); it remains to be determined in which of the afferent pathways mu receptors are found, but if they are absent from those mediating the somatosympathetic reflex and the chemoreceptor reflex, then the relative lack of effect on these reflexes would be more easily understood.…”

Section: Peptides In Cardiorespiratory Regulationmentioning

confidence: 95%

Differential regulation of the central neural cardiorespiratory system by metabotropic neurotransmitters

Pilowsky

Lung

Spirovski

et al. 2009

Phil. Trans. R. Soc. B

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Central neurons in the brainstem and spinal cord are essential for the maintenance of sympathetic tone, the integration of responses to the activation of reflexes and central commands, and the generation of an appropriate respiratory motor output. Here, we will discuss work that aims to understand the role that metabotropic neurotransmitter systems play in central cardiorespiratory mechanisms. It is well known that blockade of glutamatergic, gamma-aminobutyric acidergic and glycinergic pathways causes major or even complete disruption of cardiorespiratory systems, whereas antagonism of other neurotransmitter systems barely affects circulation or ventilation. Despite the lack of an 'all-or-none' role for metabotropic neurotransmitters, they are nevertheless significant in modulating the effects of central command and peripheral adaptive reflexes. Finally, we propose that a likely explanation for the plethora of neurotransmitters and their receptors on cardiorespiratory neurons is to enable differential regulation of outputs in response to reflex inputs, while at the same time maintaining a tonic level of sympathetic activity that supports those organs that significantly autoregulate their blood supply, such as the heart, brain, retina and kidney. Such an explanation of the data now available enables the generation of many new testable hypotheses.

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“…The autonomic regions in the thoracic and upper lumbar spinal are known to receive excitatory input from the sympathoexcitatory RVLM neurons (6,12,29,37). E-2 microinjected into the RVLM may hyperpolarize sympathoexcitatory neurons by activating -receptors located on them; the presence of -opioid receptors on bulbospinal RVLM neurons has been demonstrated by immunohistochemical studies (2). The inhibitory effect of opioids on RVLM neurons is well documented (3, 8, 13).…”

Section: Discussionmentioning

confidence: 96%

“…The presence of -opioid receptors has been reported in the general area encompassing the RVLM (2,9,20). Two tetrapeptides [endomorphin-1 and endomorphin-2 (E-2)], isolated from human cortex and bovine hypothalamus, have been reported to possess a high affinity and selectivity for the -opioid receptors and are considered to be endogenous ligands for these receptors (14,40).…”

mentioning

confidence: 99%

Attenuation of aortic baroreflex responses by microinjections of endomorphin-2 into the rostral ventrolateral medullary pressor area of the rat

Kasamatsu¹,

Sapru²

2005

American Journal of Physiology-Regulatory, Integrative and Comp

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(RVLM). This investigation was carried out to test the hypothesis that endomorphins in the RVLM may have a modulatory role in regulating cardiovascular function. Blood pressure and heart rate (HR) were recorded in urethane-anesthetized male Wistar rats. Unilateral microinjections of endomorphin-2 (0.0125-0.5 mmol/l) into the RVLM elicited decreases in mean arterial pressure (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and HR (12-36 beats/min), which lasted for 2-4 min. Bradycardia was not vagally mediated. The effects of endomorphin-2 were mediated via -opioid receptors because prior microinjections of naloxonazine (1 mmol/l) abolished these responses; the blocking effect of naloxonazine lasted for 15-20 min. Unilateral stimulations of aortic nerve for 30 s (at frequencies of 5, 10, and 25 pulses/s; each pulse 0.5 V and 1-ms duration) elicited depressor and bradycardic responses. These responses were significantly attenuated by microinjections of endomorphin-2 (0.2 and 0.4 mmol/l). The inhibitory effect of endomorphin-2 on baroreflex responses was prevented by prior microinjections of naloxonazine. Microinjections of naloxonazine alone did not affect either baseline blood pressure and HR or baroreflex responses. These results indicate that endomorphin-2 elicits depressor and bradycardic responses and inhibits baroreflex function when injected into the RVLM. These effects are consistent with the known hyperpolarizing effect of opioid peptides on RVLM neurons. bradycardia; depressor responses; naloxonazine; opioid peptides THE IMPORTANCE OF ROSTRAL ventrolateral medullary pressor area (RVLM) in the regulation of cardiovascular function is well established (12,18,29,35). Electrophysiological and anatomic evidence shows that sympathoexcitatory neurons located in the RVLM send direct monosynaptic projections to the intermediolateral cell column of the spinal cord (6, 12). It is also well known that RVLM is important in mediating the baroreceptor, chemoreceptor, and cardiopulmonary reflex responses (12,18,29,35).The presence of -opioid receptors has been reported in the general area encompassing the RVLM (2, 9, 20). Two tetrapeptides [endomorphin-1 and endomorphin-2 (E-2)], isolated from human cortex and bovine hypothalamus, have been reported to possess a high affinity and selectivity for the -opioid receptors and are considered to be endogenous ligands for these receptors (14,40). The presence of endomorphin-like immunoreactivity has been demonstrated in the general region of the RVLM (19,27). From these reports, it was hypothesized that endomorphins may play a role in the mediation and/or modulation of cardiovascular function in the RVLM. Except for one preliminary study from this laboratory (33), there is no report in the literature in which the role of endomorphins in the cardiovascular regulation at the level of RVLM has been studied in vivo. In this paper, we describe the mechanism of cardiovascular effects of E-2 in the RVLM and the effect of -opioid-receptor activation on the aortic barorefle...

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μ‐opioid receptors are present in functionally identified sympathoexcitatory neurons in the rat rostral ventrolateral medulla

Cited by 40 publications

References 49 publications

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Brown adipose tissue thermogenesis contributes to fentanyl-evoked hyperthermia

Differential regulation of the central neural cardiorespiratory system by metabotropic neurotransmitters

Attenuation of aortic baroreflex responses by microinjections of endomorphin-2 into the rostral ventrolateral medullary pressor area of the rat

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