Depression of potassium-evoked striatal acetylcholine release by δ-receptor activation: inhibition by cholinoactive agents

1988 ◽  
Vol 66 (12) ◽  
pp. 1487-1492 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Muscarinic Receptor ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Maximal Effect ◽  
Ach Release ◽  
High Potassium ◽  
Depressant Action ◽  
Δ Opioid Receptor

To examine the role of δ-opioid receptors in the modulation of striatal acetylcholine (ACh) release, the action of D-Pen2,L-Pen5-enkephalin, a selective δ-opioid receptor agonist, was tested on [3H]ACh release from slices of the rat caudate–putamen. Slices, incubated with [3H]choline, were superfused with a physiological buffer and stimulated twice by exposure to a high potassium (K+) concentration. In the absence of a cholinesterase inhibitor, 1 μM D-Pen2,L-Pen5-enkephalin produced a 46 and 35% decrease in the release of [3H]ACh evoked by 15 and 25 mM K+, respectively. The depressant action of the enkephalin analogue was concentration dependent, with a maximal effect on K+-evoked [3H]ACh release occurring at 1.0 μM, and was completely blocked in the presence of the δ-opioid receptor selective antagonist, ICI 174864 (1 μM). In the presence of the cholinesterase inhibitors physostigmine (10 μM) and neostigmine (10 μM), or the muscarinic receptor agonist oxotremorine (10 μM), D-Pen2,L-Pen5-enkephalin did not depress the K+-evoked release of [3H]ACh. Atropine (1 μM) blocked the inhibitory effect of physostigmine on the depressant action of D-Pen2,L-Pen5-enkephalin. The results of this study indicate that δ-opioid receptor activation is associated with an inhibition of striatal ACh release, but this opioid–cholinergic interaction is not apparent under conditions of presynaptic muscarinic receptor activation.

The K+-evoked release of [3H]acetylcholine from slices of rat globus pallidus: modulation by δ-opioid receptors

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Globus Pallidus ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Release Of Acetylcholine ◽  
Δ Opioid Receptor ◽  
Tritium Release

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.

Presynaptic A1 inhibitory/A2A facilitatory adenosine receptor activation balance depends on motor nerve stimulation paradigm at the rat hemidiaphragm

1996 ◽  
Vol 76 (6) ◽  
pp. 3910-3919 ◽  
Author(s):  
P. Correia-de-Sa ◽  
M. A. Timoteo ◽  
J. A. Ribeiro
Keyword(s):  
Nerve Stimulation ◽  
High Frequency ◽  
Receptor Agonist ◽  
Motor Nerve ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
Ach Release ◽  
A2a Receptor ◽  
Synaptic Control

1. Adenosine modulates acetylcholine (ACh) release from the rat motor nerve terminals. Tonic activation of presynaptic A1 inhibitory and/or A2A facilitatory adenosine receptors is regulated by the concentration of the nucleoside at the synapse. The parameters (frequency, duration of pulses, train length) of nerve stimulation determine the amount of transmitter and/or modulator released, and have long been proposed as important features of synaptic control. This prompted us to investigate which was the prevailing response to adenosine on evoked [3H]-ACh release from rat phrenic nerve hemidiaphragm preparations in different stimulation conditions. 2. With low-frequency, short-duration pulses (5 Hz, 40 microseconds in duration), the adenosine inhibitory tonus (approximately 30%) predominates. The magnitude of the adenosine tonic inhibition was dependent on the number of pulses (250–750) delivered in each stimulation train, e.g., the facilitatory effect of adenosine deaminase (ADA, 0.5 U/ml) and the inhibitory effect of the adenosine uptake blocker S-(p-nitrobenzyl)-6-thioinosine (NBTI, 5 microM) reached significance only when > 250 pulses were applied. Facilitation was only observed with high concentrations of either exogenous adenosine (> 100 microM) or NBTI (> 10 microM). 3. When the stimulation pulse duration was increased to 1 ms (5 Hz, 750 pulses), endogenously generated adenosine consistently facilitated evoked [3H]-ACh release. In these conditions, ADA (0.5 U/ml) decreased evoked [3H]-ACh release by 29 +/- 4% (mean +/- SE) (n = 3), and both NBTI (3-30 microM) and adenosine (10–500 microM), which had biphasic effects with pulses of 40 microseconds, facilitated transmitter release. 4. When high-frequency “trains” (50 Hz, 40 microseconds, 500 pulses) were applied, both ADA (0.5 U/ml) and NBTI (5 microM) failed to modify evoked [3H]-ACh release. To bypass putative feedforward inhibition of ecto-5'-nucleotidase induced by released ATP, which might reduce adenosine formation during high-frequency trains, experiments containing a series of five high-frequency “bursts” (50 Hz, 40 microseconds, 100 pulses) with variable interburst intervals (5–20 s) were performed. In such conditions, the prevailing tonic response to adenosine turned out to be facilitatory, because ADA (0.5 U/ml) inhibited and NBTI (5 microM) facilitated evoked [3H]-ACh release. The magnitude of the inhibitory effect of ADA (0.5 U/ml) ranged from -9 +/- 6% (n = 4) to -54 +/- 8% (n = 5) as the interburst interval changed from 5 to 20 s, respectively. 5. Prolongation of individual pulses from 40 microseconds to 1 ms (5 Hz frequency) or increasing the frequency of stimulation (1–50 Hz, 40 microseconds) did not significantly change the excitatory effect of the A2A receptor agonist 2-[4-(2-p-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680C). In contrast, the inhibitory effect of the A1 receptor agonist R-N6-phenylisopropyladenosine was significantly attenuated in both stimulation conditions. 6. In conclusion, the results suggest that high-intensity, high-frequency motor nerve stimulation critically influences endogenous adenosine formation and the A1/A2A receptor activation balance, i.e., it potentiates the tonic adenosine A2A-receptor-mediated facilitation of ACh release, whereas activation of the inhibitory A1 receptors becomes less effective. A model is proposed that attempts to further elucidate adenosine's involvement in synaptic transmission adaptation.

Opioids modulate N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons

1996 ◽  
Vol 76 (3) ◽  
pp. 2093-2096 ◽  
Author(s):  
X. M. Wang ◽  
S. S. Mokha
Keyword(s):  
Nmda Receptor ◽  
Dorsal Horn ◽  
Aspartic Acid ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Receptor Activation ◽  
Evoked Responses ◽  
Nociceptive Neurons ◽  
Nociceptive Transmission ◽  
Opioid Receptor Agonist

1. The present study investigated opioid-mediated modulation of N-methyl-D-aspartic acid (NMDA)-evoked responses of trigeminothalamic neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in rats anesthetized with urethane. 2. Microiontophoretic application of NMDA activated 18/19 trigeminothalamic neurons. Administration of [D-Ala2, N-Me-Phe4,Gly5-ol]-Enkephalin, a selective mu-opioid receptor agonist, reduced the NMDA-evoked responses in 77% of trigeminothalamic neurons. [D-Pen2,5]-Enkephalin, a selective delta-opioid receptor agonist, produced inhibition of NMDA-evoked responses in 36% of neurons. 3. We suggest that 1) NMDA-receptor activation excites trigeminothalamic nociceptive neurons and may, therefore, mediate nociceptive transmission in the medullary dorsal horn; and 2) the predominantly inhibitory modulation of NMDA-receptor-mediated responses of nociceptive trigeminothalamic neurons by activation of mu- and delta-opioid receptors may provide a neural mechanism for the antinociceptive actions of opioids.

Behavioral effects of benzylideneoxymorphone (BOM), a low efficacy µ opioid receptor agonist and a δ opioid receptor antagonist

2020 ◽  
Vol 237 (12) ◽  
pp. 3591-3602
Author(s):  
Sanjana Mada ◽  
Lisa R. Gerak ◽  
Amélie Soyer ◽  
David R. Maguire ◽  
Zehua Hu ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Behavioral Effects ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

scholarly journals TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/oproteins and KATPchannels

1998 ◽  
Vol 274 (3) ◽  
pp. H909-H914 ◽  
Author(s):  
Jo El J. Schultz ◽  
Anna K. Hsu ◽  
Hiroshi Nagase ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Cardioprotective Effect ◽  
Area At Risk ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

We have previously shown that delta (δ)-opioid receptors, most notably δ1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which δ-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/oproteins are involved in the cardioprotective effect produced by δ1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating δ1-opioid receptors produces cardioprotection, TAN-67, a new selective δ1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective δ1-antagonist, before TAN-67. To study the involvement of KATPchannels or Gi/oproteins in δ1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATPchannel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/oproteins, was administered before TAN-67. Infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR as compared with control (56 ± 2 to 27 ± 5%, n = 5, P < 0.05). The cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX (51 ± 3, 53 ± 5, and 61 ± 4%, n = 6 for each group, respectively). These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/oproteins and KATPchannels in the intact rat heart.

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