Developmental changes in the behavioral and autonomic effects of kappa opioid receptor stimulation of the midbrain periaqueductal gray

Although kappa- and delta-opioid receptors on mammalian cardiac myocytes have been discovered recently, the intracellular effects that result from stimulation of these receptors remain unknown. We examine the effects of a rapid and brief exposure to a kappa-opioid receptor agonist on intracellular Ca2+, pH, and cell length in individual isolated rat ventricular cells. The specific kappa-agonist trans-dl-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide (U-50488H) (methane sulfonate salt) caused a transient increase in cytosolic pH (pHi) measured from the change in SNARF-1 fluorescence and an increase in cytosolic [Ca2+] (Cai), indexed by a change in indo-1 fluorescence. The initial Cai increase often was followed by Cai oscillations. Both pHi and Cai effects were blocked by the specific antagonist kappa-opioid receptor l-(N-furylmethyl)-alpha-normetazocine methane-sulfonate (Mr 1452). The amplitude of contraction that accompanied the Cai increase elicited by U-50488H was greater than that associated with a similar increase in Cai elicited by electrical stimulation or by the rapid exposure of cells to caffeine. Thus an acute and brief kappa-opioid receptor stimulation of cardiac cells leads to an increase in Cai and pHi. The pHi increase was abolished by 1) blockade of the Na(+)-H+ exchanger by ethyl isopropyl amiloride and 2) inhibition of protein kinase C (PKC) activity via pretreatment with staurosporine or prolonged incubation with 4 beta-phorbol 12-myristate 13-acetate. These maneuvers did not abolish the U-50488H-induced increase in Ca.(ABSTRACT TRUNCATED AT 250 WORDS)

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Behavioral effects of kappa-opioid-receptor stimulation on neonatal rats.

Behavioral Neuroscience ◽

10.1037/0735-7044.108.2.418 ◽

1994 ◽

Vol 108 (2) ◽

pp. 418-423 ◽

Cited By ~ 30

Author(s):

Priscilla Kehoe ◽

Carolyn B. Boylan

Keyword(s):

Opioid Receptor ◽

Kappa Opioid Receptor ◽

Behavioral Effects ◽

Neonatal Rats ◽

Kappa Opioid ◽

Receptor Stimulation

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The KCa channel as a trigger for the cardioprotection induced by kappa-opioid receptor stimulation - its relationship with protein kinase C

British Journal of Pharmacology ◽

10.1038/sj.bjp.0706268 ◽

2005 ◽

Vol 145 (7) ◽

pp. 984-991 ◽

Cited By ~ 27

Author(s):

Chun-Mei Cao ◽

Mai Chen ◽

Tak-Ming Wong

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Opioid Receptor ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Receptor Stimulation ◽

Kinase C

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Kappa opioid receptor modulation on GABAergic inputs onto ventral periaqueductal gray dopamine neurons

10.1101/389536 ◽

2018 ◽

Author(s):

Chia Li ◽

Thomas L. Kash

Keyword(s):

Opioid Receptor ◽

Periaqueductal Gray ◽

Kappa Opioid Receptor ◽

Dopamine Neurons ◽

Kappa Opioid ◽

Specific Population ◽

Receptor Modulation ◽

Mechanism Of Inhibition ◽

Altered Regulation ◽

The Impact

AbstractThe kappa opioid receptor (KOR) system has been implicated in regulation of many behaviors including pain. While there are numerous studies suggesting KOR-regulation of pain being mediated spinally, there have been reports of pain-like behaviors regulated by central KOR signaling. In particular, oxytocin-induced analgesia appears to be mediated by KOR receptors within the ventrolateral periaqueductal gray (vlPAG). The vlPAG is a brain region that has long been known to be involved in the regulation of pain. We recently found that dopamine (DA) neurons within the vlPAG represent a specific population of neurons that can regulate pain-like behaviors. In this study, we sought to determine the impact of KOR signaling on GABAergic inputs to the vlPAG DA neurons, and determine the mechanism of inhibition. We found that activation of KOR significantly reduced GABAergic transmission onto vlPAG DA neurons. In addition, our data suggest this effect is mediated pre-synaptically via the G-protein βγ subunit. These data suggest the possibility that KOR-activation disinhibits vlPAG dopamine neurons, which could lead to altered regulation of pain-related behaviors.

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