Central opioid receptors mediate glucoprivic inhibition of pituitary LH secretion

1997 ◽  
Vol 272 (4) ◽  
pp. E517-E522 ◽  
Author(s):  
K. P. Briski
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Hormone Secretion ◽  
Male Rats ◽  
Pituitary Hormone ◽  
Intracerebroventricular Administration ◽  
Receptor Antagonists ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Antagonists

The present studies investigated the significance of glucoprivic metabolic signals, particularly those of central origin, to the regulation of pituitary luteinizing hormone (LH). Groups of gonadectomized (GDX) adult male rats were treated with 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, by either intravenous (50, 100, or 200 mg/kg) or intracerebroventricular (5, 20, or 100 microg/rat) administration. Systemic drug treatment caused a significant decrease in mean plasma LH levels compared with saline-treated controls. Intracerebroventricular administration of 2-DG was also efficacious in suppressing circulating LH; animals treated with either of the two highest doses of the drug exhibited a significant reduction in plasma LH. In vitro studies examined direct effects of 2-DG on pituitary gonadotrope secretory activity. Exposure of anterior pituitary tissue to 2-DG during short-term perfusion had no significant impact upon either basal or gonadotropin-releasing hormone-stimulated LH release. Finally, groups of GDX rats were pretreated by intracerebroventricular administration of either the nonselective opioid receptor antagonist, naltrexone, or the selective mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA), before intravenous injection of 2-DG. Both receptor antagonists were observed to attenuate the suppressive effects of 2-DG on circulating LH in these animals. In summary, treatment of GDX rats with the glucose antimetabolite, 2-DG, decreased plasma LH, suggesting that metabolic signaling of cellular glucose oxidation is of physiological importance to the regulation of pituitary hormone secretion. Findings that plasma LH was diminished in animals treated intracerebroventricularly with 2-DG implicate central glucoprivic receptors in neuroendocrine mechanisms governing the reproductive endocrine axis. Attenuation of 2-DG-induced decreases in circulating LH by opioid receptor antagonists suggests that these receptors, particularly the mu-subtype, mediate central effects of glucoprivation on circulating LH.

Endogenous Activation of Supraoptic Nucleus κ-Opioid Receptors Terminates Spontaneous Phasic Bursts in Rat Magnocellular Neurosecretory Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 3235-3244 ◽  
Author(s):  
Colin H. Brown ◽  
Gareth Leng ◽  
Mike Ludwig ◽  
Charles W. Bourque
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Random Element ◽  
Plateau Potentials ◽  
Phasic Activity ◽  
Potential Amplitude ◽  
Opioid Receptor Antagonist ◽  
Plateau Potential ◽  
Dynorphin Release

Phasic activity in magnocellular neurosecretory vasopressin cells is characterized by alternating periods of activity (bursts) and silence. During phasic bursts, action potentials (spikes) are superimposed on plateau potentials that are generated by summation of depolarizing after-potentials (DAPs). Burst termination is believed to result from autocrine feedback inhibition of plateau potentials by the κ-opioid peptide, dynorphin, which is copackaged in vasopressin neurosecretory vesicles and exocytosed from vasopressin cell dendrites during phasic bursts. Here we tested this hypothesis, using intracellular recording in vitro to show that κ-opioid receptor antagonist administration enhanced plateau potential amplitude to increase postspike excitability during spontaneous phasic activity. The antagonist also increased postburst DAP amplitude in vitro, indicating that endogenous dynorphin probably reduces plateau potential amplitude by inhibiting the DAP mechanism. However, the κ-opioid receptor antagonist did not affect the slow depolarization that follows burst termination, suggesting that recovery from endogenous κ-opioid inhibition does not contribute to the slow depolarization. We also show, by extracellular single-unit recording, that that there is a strong random element in the timing of burst initiation and termination in vivo. Administration of a κ-opioid receptor antagonist eliminated the random element of burst termination but did not alter the timing of burst initiation. We conclude that dendritic dynorphin release terminates phasic bursts by reducing the amplitude of plateau potentials to reduce the probability of spike firing as bursts progress. By contrast, dendritic dynorphin release does not greatly influence the membrane potential between bursts and evidently does not influence the timing of burst initiation.

scholarly journals A TWO-YEAR STUDY OF CANCEROGENIC POTENTIAL OF THE NEW OPIOID RECEPTOR ANTAGONIST ONDELOPRAN IN RATS

2019 ◽  
Vol 6 (2) ◽  
pp. 58-68
Author(s):  
K. L. Kryshen ◽  
A. A. Muzhikyan ◽  
D. S. Gaidai ◽  
K. O. Zaikin ◽  
A. E. Katelnikova ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Test Item ◽  
Clinical Signs ◽  
The Body ◽  
Starch Solution ◽  
Opioid Receptor Antagonist ◽  
Age Related ◽  
Opioid Receptor Antagonists ◽  
Inner Organs

Opioid receptor antagonists are widely used for the treatment of alcohol dependence. Currently, original drug Odelepran (INN: ondelopran) with a unique binding profi le to all three types of human opioid receptors (μ, κ, δ) is being developed by R-Pharm.Aim of the study. To investigate a cancerogenic poten… al of the new opioid receptor antagonist ondelopran in a twoyear study in rats Materials and methods. The study cancerogenic potencial was performed in male and female Wistar rats at the age of 8–10 weeks at the start of experiment. All animals were allocated to 8 groups. Each group consisted of 50 animals of each sex. Test item (ondelopran fi lm-coated tablets, 125 mg), was administered to the animals intragastrically as a tablets suspension in 1% starch solution daily, 5 days a week for 24 months in two doses: 10 mg/kg (equivalent therapeutic dose for humans) and 100 mg/kg. Animals of control groups were administered with placebo and vehicle (1% starch solution). Clinical observation and examination of animals were conducted weekly to detect any signs of intoxication; dynamics of the body weight and registration of animal deaths were also assessed. To assess the rate of the pathological changes, the macro- and microscopic examina… on of inner organs and neoplasms was conducted.Results. During the study the mortality rates did not diff er between the groups. Clinical signs ts.and symptoms of intoxication upon administration of the tested item and placebo were not observed. Neoplasms were found in the organs of all groups of animals. More than 30 variants of neoplasms were identifi ed upon pathomorphological examination. The identifi ed tumors are typical for rats and considered as spontaneous age-related pathology. There was no statistically signifi cant diff erences between groups in the total incidence of tumors.Conclusion. To conclude the above said, the test item of the ondelopran fi lm-coated tablets, 125 mg have no carcinogenic properties.

Long-Term Potentiation in Direct Perforant Path Projections to the Hippocampal CA3 Region In Vivo

2002 ◽  
Vol 87 (2) ◽  
pp. 669-678 ◽  
Author(s):  
Viet H. Do ◽  
Carlo O. Martinez ◽  
Joe L. Martinez ◽  
Brian E. Derrick
Keyword(s):  
Nmda Receptor ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Hippocampal Formation ◽  
Nmda Receptor Antagonist ◽  
Perforant Path ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Antagonists ◽  
Μ Opioid Receptor ◽  
Ca3 Region

The perforant path constitutes the primary projection system relaying information from the neocortex to the hippocampal formation. Long-term synaptic potentiation (LTP) in the perforant path projections to the dentate gyrus is well characterized. However, surprisingly few studies have addressed the mechanisms underlying LTP induction in the direct perforant path projections to the hippocampus. Here we investigate the role of N-methyl-d-aspartate (NMDA) and opioid receptors in the induction of LTP in monosynaptic medial and lateral perforant path projections to the CA3 region in adult pentobarbital sodium–anesthetized rats. Similar to LTP observed at the medial perforant path–dentate gyrus synapse, medial perforant path–CA3 synapses display LTP that is blocked by both local and systemic administration of the competitive NMDA receptor antagonist (±)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid [(±)-CPP]. By contrast, LTP induced at the lateral perforant path–CA3 synapses is not blocked by either local or systemic administration of this NMDA receptor antagonist. The induction of LTP at lateral perforant path–CA3 synapses, which is blocked by the opioid receptor antagonist naloxone, is also blocked by the selective mu (μ) opioid receptor antagonist Cys2-Tyr3-Orn5-Pen7-amide (CTOP), but not the selective delta (δ) opioid receptor antagonist naltrindole (NTI). CTOP was without effect on the induction of medial perforant path–CA3 LTP. The selective sensitivity of lateral perforant path–CA3 LTP to μ-opioid receptor antagonists corresponds with the distribution of μ-opioid receptors within the stratum lacunosum-moleculare of area CA3 where perforant path projections to CA3 terminate. These data indicate that both lateral and medial perforant path projections to the CA3 region display LTP, and that LTP induction in medial and lateral perforant path–CA3 synapses are differentially sensitive to NMDA receptor and μ-opioid receptor antagonists. This suggests a role for opioid, but not NMDA receptors in the induction of LTP at lateral perforant path projections to the hippocampal formation.

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