Depression of potassium-evoked striatal acetylcholine release by delta-receptor activation: inhibition by cholinoactive agents.
To examine the role of delta-opioid receptors in the modulation of striatal acetylcholine (ACh) release, the action of D-Pen2,L-Pen5-enkephalin, a selective delta-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 microM 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 microM, and was completely blocked in the presence of the delta-opioid receptor selective antagonist, ICI 174864 (1 microM). In the presence of the cholinesterase inhibitors physostigmine (10 microM) and neostigmine (10 microM), or the muscarinic receptor agonist oxotremorine (10 microM), D-Pen2,L-Pen5-enkephalin did not depress the K+-evoked release of [3H]ACh. Atropine (1 microM) blocked the inhibitory effect of physostigmine on the depressant action of D-Pen2,L-Pen5-enkephalin. The results of this study indicate that delta-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.
Ruzicka
B B
BB
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
Jhamandas
K
K
D000109:Acetylcholine / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017465:Receptors, Opioid, delta
D000700:Analgesics; D004745:Enkephalins; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D009388:Neostigmine; D010095:Oxotremorine; D020881:Enkephalin, D-Penicillamine (2,5)-; D010830:Physostigmine; D000109:Acetylcholine; D011188:Potassium