Immunohistochemical localization of the cloned κ1 receptor in the rat CNS and pituitary

Mansour, Alfred; Burke, Sharon; Pavlic, Robert; Akil, Huda; Watson, Stanley J.

doi:10.1016/0306-4522(95)00464-5

Cited by 138 publications

(90 citation statements)

References 50 publications

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“…This subpopulation of neurons express KORs postsynaptically that may exert a powerful but selective inhibition of NTS neurons. In the caudal NTS dense KOR1 immunoreactivity has been demonstrated in axons (Mansour et al 1996), indicating a predominantly presynaptic site of action which fits with our findings of few postsynaptic receptor mediated responses. In keeping with this, we have also shown that U69593 reduced the amplitude and increased the paired pulse ratio of EPSPs in ϳ50% of NTS neurons suggesting a more widespread distribution of presynaptic KORs.…”

Section: Kappa Agonist U69593 Has Pre-and Postsynaptic Effects In Thesupporting

confidence: 91%

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Poole

Deuchars²,

Lewis³

et al. 2007

Journal of Neurophysiology

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Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to determine whether responses of neurons to activation of opioid receptors were dependent on their location within the NTS. Using whole cell patch-clamp recordings from neurons within the NTS, the mu opioid receptor (MOR) agonist [D-Ala 2 , N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO, 100 nM) hyperpolarized a proportion of neurons in the medial, dorsomedial and dorsolateral NTS, whereas no postsynaptic responses were observed in remaining subdivisions. DAMGO reduced the amplitude of solitary tract-evoked excitatory postsynaptic potentials (EPSPs) in all neurons tested, regardless of subdivision. The kappa opioid receptor (KOR) agonist U69593 (10 -20 M) also hyperpolarized a small fraction of neurons (6/79) and decreased the amplitude of EPSPs in 50% of neurons. In contrast, the delta-opioid receptor agonist DPDPE (1-4 M) had no presynaptic or postsynaptic effects on NTS neurons even after preincubation with bradykinin. Anatomical data at the light and electron microscopic level complemented electrophysiological observations with respect to MOR location and further showed that MORs were present at both presynaptic and postsynaptic sites in the dorsolateral NTS, often at the same synapse. These data demonstrate site specific responses of neurons to activation of MORs and KORs, which may underlie their ability to modulate different autonomic reflexes.

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Section: Kappa Agonist U69593 Has Pre-and Postsynaptic Effects In Thesupporting

confidence: 91%

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Poole

Deuchars²,

Lewis³

et al. 2007

Journal of Neurophysiology

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“…Although no direct response to hypocretin is found in hypocretin neurons , the opioid peptide dynorphin that is cosynthesized in hypocretin cells in both human and rodent (Chou et al, 2001;Crocker et al, 2005) exerts a substantive and direct inhibition of hypocretin neurons by multiple mechanisms, causing a reduction in spike frequency, hyperpolarization, an activation of GIRK currents, a reduction in calcium currents, and a presynaptic inhibition of synaptic glutamate release. Nor-BNI blocks the direct actions, suggesting they are mediated by receptors expressed by hypocretin neurons, consistent with previous reports of receptor expression in the lateral hypothalamus (Mansour et al, 1994(Mansour et al, , 1996. Of considerable interest, when the receptor antagonist (without exogenous dynorphin) was applied to the slice, an increase in neuronal activity was found.…”

Section: Dynorphin Inhibits Hypocretin Neuronssupporting

confidence: 89%

Differential Target-Dependent Actions of Coexpressed Inhibitory Dynorphin and Excitatory Hypocretin/Orexin Neuropeptides

Liu¹,

Pol²

2006

J. Neurosci.

133

134

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The hypocretin/orexin arousal system plays a key role in maintaining an alert wake state. The hypocretin peptide is colocalized with an opioid peptide, dynorphin. As dynorphin may be coreleased with hypocretin, we asked what action simultaneous stimulation with the excitatory neuropeptide hypocretin and the inhibitory peptide dynorphin might exert on cells postsynaptic to hypocretin axons, including hypocretin neurons. Hypocretin neurons received direct synaptic contact from other hypocretin neurons but showed little direct response to hypocretin. Here, we show that mouse hypocretin neurons are acutely sensitive to dynorphin. Dynorphin inhibits the hypocretin system by direct postsynaptic actions (hyperpolarization, decreased spike frequency, increased GIRK (G-protein-gated inwardly rectifying K ϩ channel) current, and attenuated calcium current, and indirectly by reducing excitatory synaptic tone. Interestingly, a selective antagonist of -opioid receptors enhanced activity of the hypocretin system, suggesting ongoing depression by endogenous hypothalamic opioids. Electrical stimulation of hypothalamic microslices that contained hypocretin cells and their axons evoked dynorphin release. Costimulation with dynorphin and hypocretin had three different effects on neurons postsynaptic to hypocretin axons: direct response to only one or the other of the two peptides [hypocretin cells respond to dynorphin, arcuate neuropeptide Y (NPY) cells respond to hypocretin], differential desensitization causing shift from inhibitory current to excitatory current with repeated coexposure (melanin-concentrating hormone neurons), synergistic direct excitation by hypocretin and presynaptic attenuation of inhibition by dynorphin (arcuate NPY neurons). These results suggest that hypocretin neurons may be able to exercise a high degree of modulatory control over postsynaptic targets using multiple neuropeptides with target-dependent actions.

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“…Immunohistochemistry and in situ hybridization studies have congruously demonstrated that distribution of the PDYN gene products is quite widespread in the mammalian nervous system and very similar to that of KOR (Mansour et al, 1988;Mansour et al, 1996;Merchenthaler et al, 1997). α-Neo, Dyn A and Dyn B have similar distribution in the central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Dynorphin peptides differentially regulate the human κ opioid receptor

Chen

Liu‐Chen

2007

Life Sciences

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Dynorphins, endogenous peptides for the κ opioid receptor, play important roles in many physiological and pathological functions. Here, we examined how prolonged treatment with three major prodynorphin peptides, dynorphin A (1-17) (Dyn A), dynorphin B (1-13) (Dyn B) and α-neoendorphin (α-Neo), regulated the human kappa opioid receptor (hKOR) stably expressed in Chinese hamster ovary (CHO) cells. Results from receptor binding and [ 35 S]GTPγS binding assays showed that these peptides were potent full agonists of the hKOR with comparable receptor reserve and intrinsic efficacy to stimulate G proteins. A 4-h incubation with α-Neo at a concentration of ∼600× EC 50 value (from [ 35 S]GTPγS binding) resulted in receptor down-regulation to a much lower extent than the incubation with Dyn A and Dyn B at comparable concentrations (∼10% vs. ∼65%). Extending incubation period and increasing concentrations did not significantly affect the difference. The plateau level of α-Neo-mediated receptor internalization (30 min) was significantly less than those of Dyn A and Dyn B. Omission of serum from the incubation medium or addition of peptidase inhibitors into the serum-containing medium enhanced α-Neo-, but not Dyn A-or Dyn B-, mediated receptor down-regulation and internalization; however, the degrees of α-Neo-induced adaptations were still significantly less than those of Dyn A and Dyn B. Thus, these endogenous peptides differentially regulate KOR after activating the receptor with similar receptor occupancy and intrinsic efficacy. Both stability in the presence of serum and intrinsic capacity to promote receptor adaptation play roles in the observed discrepancy among the dynorphin peptides.

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Immunohistochemical localization of the cloned κ1 receptor in the rat CNS and pituitary

Cited by 138 publications

References 50 publications

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Differential Target-Dependent Actions of Coexpressed Inhibitory Dynorphin and Excitatory Hypocretin/Orexin Neuropeptides

Dynorphin peptides differentially regulate the human κ opioid receptor

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