FREQUENCY-DEPENDENT MUSCARINIC RECEPTOR MODULATION OF ACETYLCHOLINE AND DOPAMINE RELEASE FROM RABBIT STRIATUM

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (1) , 98-104
Abstract
The effects of muscarinic receptor activation on the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) or [3H]ACh were investigated in rabbit striatal slices. Release was measured in the presence of 10 .mu.M hemicholinium and 1 .mu.M sulpiride to block choline uptake and prevent the effects of released DA on DA receptors modulating release. Stimulation (120 pulses, 20 mA, 2 ms) at 0.3, 3 and 10 Hz produced (3H or 14C) ACh release that sharply declined with increasing stimulation frequency. A flat frequency-release curve was obtained for DA. Oxotremorine (OXO), a direct muscarinic agonist (1-100 .mu.M), produced a concentration-dependent inhibition of ACh release, inversely related to stimulation frequency, at a fixed number of pulses (120). When the number of pulses was modified to produce similar amounts of ACh release (20 pulses at 0.1 Hz, 39 pulses at 0.3 Hz, 120 pulses at 3 Hz and 350 pulses at 10 Hz), much greater inhibition of ACh release by OXO (0.3 and 3 .mu.M) was obtained with lower frequencies and lower number of pulses. Physostigmine, an acetylcholinesterase inhibitor, decreased ACh release with an inverse relationship to stimulation frequency. Atropine (1 .mu.M), a selective muscarinic antagonist, enhanced the release of ACh more at 10 Hz than at 0.3 and 3 Hz and completely antagonized the effects of OXO (10 .mu.M) and physostigmine (1 .mu.M) at all 3 stimulation frequencies. OXO (3 and 10 .mu.M) enhanced DA release at 3 Hz. Physostigmine (1 .mu.M) and atropine (1 .mu.M) had no effect on DA release. In the rabbit striatum, muscarinic receptors may regulate ACh release, whereas they do not seem to play a significant role in the modulation of DA release. Because of high cholinesterase activity, the release of ACh evoked by low rates of stimulation is not subject to inhibitory modulation of release. Activation of muscarinic autoreceptors that modulate ACh release occurs at high stimulation frequencies or in the presence of cholinesterase inhibition. The effects of muscarinic agonists and antagonists on ACh release are highly dependent on the frequency of stimulation.

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