Dual synaptic effects of activating M1-muscarinic receptors, in superior cervical ganglia of rabbits.
Postsynaptic potentials elicited by various muscarinic agonists and by preganglionic stimuli in the presence of such agonists were recorded from rabbit superior cervical ganglia using sucrose-gap and air-gap methods. While methacholine and bethanechol (both at 10(-4) M) induced biphasic potential changes, McN-A-343 and a novel synthetic compound AF-102B (10(-7) M-10(-5) M) produced only a depolarizing response which was depressed by the M1-antagonist pirenzepine (10(-7) M), but not by the M2 antagonist AF-DX 116 (same concentration), indicating that these compounds act purely as M1-muscarinic agonists in this system. These agonists selectively depressed the orthodromic slow excitatory postsynaptic potential (EPSP) in a dose-dependent manner without substantially affecting the fast EPSP; this is in accord with the view that their depolarizing action is on the same postsynaptic muscarinic receptor that mediates the slow EPSP. The slow inhibitory post synaptic potential (IPSP), on the other hand, was found potentiated in the presence of these agonists. This potentiation was antagonized not only by pirenzepine but also by yohimbine; the potentiation was itself enlarged by nomifensine (a dopamine-uptake inhibitor). We postulate that M1-muscarinic receptors are present not only on the postganglionic principal cells but also on the interneurons; the former were already known to be responsible for the generation of slow EPSP, but the latter may be on terminals of dopamine-containing small intensely fluorescent cells and regulate the orthodromic release of dopamine and are to be distinguished from the M2-receptors.
Mochida
S
S
Department of Physiology, Tokyo Medical College, Japan.
Mizobe
F
F
Fisher
A
A
Kawanishi
G
G
Kobayashi
H
H
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D014403:Tubocurarine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011812:Quinuclidines; D011976:Receptors, Muscarinic; D015016:Yohimbine; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D014403:Tubocurarine