Muscarinic modulation of neurotransmission: the effects of some agonists and antagonists.
1. Functional studies were performed to evaluate the effects of some muscarinic agents at the neuromuscular junction of the mouse. 2. The presynaptic control of acetylcholine release and the postsynaptic activation of the nicotinic receptor have been analyzed by means of extracellular recording. The amplitude of spontaneous and of evoked acetylcholine release, the frequency of spontaneous acetylcholine release and the time course of the quantal release have been measured by means of an EPC7 patch clamp amplifier. 3. This electrophysiological method revealed multiple dose-related effects of some agonists and antagonists on the above parameters. Concentration-response curves related to the parameters underlying the function of this cholinergic synapse were obtained and the apparent EC50 values calculated. 4. Many of the interactions of the agonists and antagonists could inhibit neuromuscular transmission. The rank order potencies related to the inhibition of the evoked signals were carbachol > oxotremorine > d,l-muscarine for the agonists and methoctramine > 4-DAMP > l-hyoscyamine > AFDX-116 > ipratropium > pirenzepine for the antagonists. 5. These findings suggest a more complicated pattern related to the muscarinic action at the mouse neuromuscular junction with the involvement of some post-synaptic located sites.
Re
L
L
Institute of Experimental and Clinical Medicine, University of Ancona, Italy.
Cola
V
V
Fulgenzi
G
G
Marinelli
F
F
Concettoni
C
C
Rossini
L
L
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009045:Motor Endplate / Q000187:drug effects; D018727:Muscarinic Antagonists; D009469:Neuromuscular Junction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012132:Respiratory Muscles / Q000187:drug effects / Q000294:innervation; D009435:Synaptic Transmission / Q000187:drug effects*
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D000109:Acetylcholine