Kappa opioid agonists alter dopamine markers and cocaine-stimulated locomotor activity

Although several studies indicate that kappa-opioid agonists induce a water diuresis by inhibiting vasopressin (AVP) secretion, the locus of the kappa-receptors (neurohypophysial vs. hypothalamic) responsible for this effect remains unclear. We have ascertained the effect of the selective kappa-agonist BRL-52656 (BRL) on AVP secretion by using compartmentalized rat hypothalamoneurohypophysial explants in culture. When applied to the hypothalamus, nanomolar concentrations of BRL inhibited osmotically stimulated AVP secretion. This response was blocked by the highly selective kappa-opioid antagonist nor-binaltorphimine (BNI). However, osmotically stimulated AVP release was suppressed at the neurohypophysial site only by 100 nM BRL and was not reversed by BNI but only by naloxone. This dose of BRL, administered to the posterior pituitary compartment, did not appear to act by the agonist gaining access to hypothalamic kappa-opiate receptors, because BNI added to the hypothalamus failed to prevent the inhibition of AVP secretion. The data demonstrate that BRL is a potent inhibitor of osmotically stimulated AVP secretion via activation of kappa-opiate receptors within the hypothalamus, but that higher concentrations of the drug may also stimulate non-kappa-neurohypophysial opiate receptors that suppress AVP release.

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Therapeutic Potential of Kappa Opioid Agonists

Pharmaceuticals ◽

10.3390/ph12020095 ◽

2019 ◽

Vol 12 (2) ◽

pp. 95 ◽

Cited By ~ 8

Author(s):

Tyler C. Beck ◽

Matthew A. Hapstack ◽

Kyle R. Beck ◽

Thomas A. Dix

Keyword(s):

Therapeutic Potential ◽

Inflammatory Diseases ◽

Cartilage Degeneration ◽

Review Article ◽

Research Articles ◽

Original Research ◽

Kappa Opioid ◽

Opioid Agonists ◽

Novel Drugs ◽

Post Traumatic

Many original research articles have been published that describe findings and outline areas for the development of kappa-opioid agonists (KOAs) as novel drugs; however, a single review article that summarizes the broad potential for KOAs in drug development does not exist. It is well-established that KOAs demonstrate efficacy in pain attenuation; however, KOAs also have proven to be beneficial in treating a variety of novel but often overlapping conditions including cardiovascular disease, pruritus, nausea, inflammatory diseases, spinal anesthesia, stroke, hypoxic pulmonary hypertension, multiple sclerosis, addiction, and post-traumatic cartilage degeneration. This article summarizes key findings of KOAs and discusses the untapped therapeutic potential of KOAs in the treatment of many human diseases.

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EVIDENCE FOR A CENTRAL OPIOID CONTROL OF RUMINATION

Canadian Journal of Animal Science ◽

10.4141/cjas84-133 ◽

1984 ◽

Vol 64 (5) ◽

pp. 13-15 ◽

Cited By ~ 8

Author(s):

Y. RUCKEBUSCH ◽

TH. BARDON

Keyword(s):

Key Words ◽

Opioid Receptor ◽

Opioid Receptors ◽

Opioid Peptides ◽

Kappa Opioid Receptor ◽

Kappa Opioid ◽

Receptor Agonists ◽

Opioid Agonists ◽

Reflex Control ◽

Opioid Receptor Agonists

Intravenous adrenaline induced reticular extracontractions and rumination within 26 sec in hay-fed, and 184 sec in cube-fed sheep. Regardless of diet, pretreatment with cerebroventricular infusion of kappa-opioid-receptor agonists enhanced this reflex. Control of rumination may involve multiple opioid-receptors, since inhibition of the reflex occurred after mu- and delta-opioid-agonists. Key words: Sheep, rumination, opioid-peptides

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