1. The mechanism of the inhibitory action of presynaptic muscarinic receptors on the release of acetylcholine from striatal cholinergic neurons is not known. We investigated how the electrically stimulated release of [3H]-acetylcholine from superfused rat striatal slices and its inhibition by carbachol are affected by specific inhibitors of voltage-operated calcium channels of the L-type (nifedipine), N-type (omega-conotoxin GVIA) and P/Q-type (omega-agatoxin IVA). 2. The evoked release of [3H]-acetylcholine was not diminished by nifedipine but was lowered by omega-conotoxin GVIA and by omega-agatoxin IVA, indicating that both the N- and the P/Q-type (but not the L-type) channels are involved in the release. The N-type channels were responsible for approximately two thirds of the release. The release was >97% blocked when both omega-toxins acted together. 3. The inhibition of [3H]-acetylcholine release by carbachol was not substantially affected by the blockade of the L- or P/Q-type channels. It was diminished but not eliminated by the blockade of the N-type channels. 4. In experiments on slices in which cholinesterases had been inhibited by paraoxon, inhibition of [3H]-acetylcholine release by endogenous acetylcholine accumulating in the tissue could be demonstrated by the enhancement of the release after the addition of atropine. The inhibition was higher in slices with functional N-type than with functional P/Q-type channels. 5. We conclude that both the N- and the P/Q-type calcium channels contribute to the stimulation-evoked release of acetylcholine in rat striatum, that the quantitative contribution of the N-type channels is higher, and that the inhibitory muscarinic receptors are more closely coupled with the N-type than with the P/Q-type calcium channels.

• MeSH
• acetylcholin metabolismus   MeSH
• agonisté muskarinových receptorů farmakologie   MeSH
• antagonisté dopaminu farmakologie   MeSH
• antagonisté muskarinových receptorů farmakologie   MeSH
• atropin farmakologie   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• cholinesterasové inhibitory farmakologie   MeSH
• domperidon farmakologie   MeSH
• haloperidol farmakologie   MeSH
• karbachol farmakologie   MeSH
• krysa rodu Rattus MeSH
• neostriatum účinky léků   metabolismus   MeSH
• omega-agatoxin IVA MeSH
• omega-konotoxin GVIA MeSH
• paraoxon farmakologie   MeSH
• pavoučí jedy farmakologie   MeSH
• peptidy farmakologie   MeSH
• receptory muskarinové účinky léků   metabolismus   MeSH
• receptory presynaptické účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• vápníkové kanály účinky léků   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• acetylcholin MeSH
• agonisté muskarinových receptorů MeSH
• antagonisté dopaminu MeSH
• antagonisté muskarinových receptorů MeSH
• atropin MeSH
• blokátory kalciových kanálů MeSH
• cholinesterasové inhibitory MeSH
• domperidon MeSH
• haloperidol MeSH
• karbachol MeSH
• omega-agatoxin IVA MeSH
• omega-konotoxin GVIA MeSH
• paraoxon MeSH
• pavoučí jedy MeSH
• peptidy MeSH
• receptory muskarinové MeSH
• receptory presynaptické MeSH
• vápníkové kanály MeSH

The mechanism by which presynaptic muscarinic autoreceptors inhibit the release of acetylcholine (ACh) from cerebrocortical cholinergic fibres has not been clarified. To test the view that muscarinic autoreceptors act by decreasing Ca2+ influx, we performed experiments in which rat cerebrocortical prisms were preloaded with (14C)choline, washed, depolarized with 14-65 mM K+ in the absence of Ca2+ and then exposed (still under depolarization) to various concentrations of Ca2+ to evoke the release of (14C)ACh. The muscarinic agonist, oxotremorine, used at a 100 microM concentration, inhibited the release of (14C)ACh by 59-86% in experiments with 14 and 26.5 mM K+ but had no significant effect at 65.5 mM K+. No systematic changes in the inhibitory effects of oxotremorine could be found at any of the K+ concentrations used when the concentration of Ca2+ was varied in the range of 0.25-4.0 mM. At 2 mM Ca2+ and K+ concentrations above 14 mM, the inhibitory effect of oxotremorine was inversely related to the concentration of K+. The inhibitory effect of oxotremorine on (14C)ACh release was not blocked by 100 microM 4-amino-pyridine. The fact that the inhibitory effect of oxotremorine could not be overcome by an increase in the concentration of Ca2+ suggests that, under the conditions used, a restriction of the influx of Ca2+ did not play a major role in the muscarinic inhibition of ACh release; rather, oxotremorine appeared to act by decreasing membrane depolarization.2+ of the Ca(2+)-voltage hypothesis of neurotransmitter release, supposing

• MeSH
• acetylcholin metabolismus   MeSH
• atropin farmakologie   MeSH
• cholin metabolismus   MeSH
• draslík farmakologie   MeSH
• krysa rodu Rattus MeSH
• mozková kůra metabolismus   MeSH
• nervová zakončení účinky léků   metabolismus   MeSH
• oxotremorin farmakologie   MeSH
• potkani Wistar MeSH
• receptory muskarinové účinky léků   metabolismus   MeSH
• receptory presynaptické účinky léků   metabolismus   MeSH
• techniky in vitro MeSH
• tetrodotoxin farmakologie   MeSH
• vápník farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholin MeSH
• atropin MeSH
• cholin MeSH
• draslík MeSH
• oxotremorin MeSH
• receptory muskarinové MeSH
• receptory presynaptické MeSH
• tetrodotoxin MeSH
• vápník MeSH