Different muscarinic receptors mediate autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat isolated perfused heart.
Experiments were carried out on rat isolated perfused hearts with both vagus nerves attached. The acetylcholine stores were labelled with [14C]-choline. The effects of muscarinic receptor antagonists on the [14C]-overflow and increase in perfusion pressure evoked by vagus nerve stimulation (10 Hz, 4-10 mA) were studied in order to determine the muscarinic receptor type involved in autoinhibition of acetylcholine release and vagally-induced vasoconstriction in the rat heart. Stimulation of the vagus nerves (1200 pulses) caused an increase in [14C]-overflow and in perfusion pressure which was significantly reduced by hexamethonium 500 mumol/l and abolished by tetrodotoxin 0.3 mumol/l or perfusion with Ca2(+)-free solution. The fractional rate of evoked [14C]-overflow per pulse upon stimulation at 10 Hz (720 pulses) was doubled in the presence of the non-selective antagonist atropine (0.01-1 mumol/l) as well as in that of the M2-selective compounds methoctramine (0.1 mumol/l) and AF-DX 116 (0.1-1 mumol/l), but remained unaffected by the M3-selective hexahydrosiladifenidol (0.1 mumol/l). The increase in perfusion pressure upon nerve stimulation was reduced by atropine (0.01 mumol/l) or hexahydrosiladifenidol (0.1 mumol/l) to approximately 50% and increased by about 50% in the presence of AF-DX 116 (0.1 mumol/l). The results show that the autoinhibition of acetylcholine release in the rat heart is mediated by M2 receptors. On the other hand, the increase in perfusion pressure upon vagus nerve stimulation is caused by a different muscarinic receptor, more sensitive to hexahydrosiladifenidol than to M2-selective antagonists.
Bognar
I T
IT
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany.
Beinhauer
B
B
Kann
P
P
Fuder
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D000109:Acetylcholine